Relation Results

Identifier	Residue	Sequence	Organism
SIGNOR-235675	Ser1100	QGCRRRHsSETFSST	Homo sapiens
pmid	sentence
17360977	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223

Identifier	Residue	Sequence	Organism
SIGNOR-236729	Ser1222	ESSSTRRsSEDLSAY	Homo sapiens
pmid	sentence
17360977	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223

Identifier	Residue	Sequence	Organism
SIGNOR-236603	Ser1223	SSSTRRSsEDLSAYA	Homo sapiens
pmid	sentence
17360977	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223

Publications:

3

Organism:

Homo Sapiens

Tissue:

Ovary

Identifier	Residue	Sequence	Organism
SIGNOR-260906	Ser1101	GCRRRHSsETFSSTP	Mus musculus
pmid	sentence
15364919	Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).

Publications:

1

Organism:

Mus Musculus

Identifier	Residue	Sequence	Organism
SIGNOR-127904	Ser1101	GCRRRHSsETFSSTP	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulates insulin.

Identifier	Residue	Sequence	Organism
SIGNOR-51216	Ser270	EFRPRSKsQSSSNCS	Homo sapiens
pmid	sentence
9312143	Turnover of the active fraction of irs1 involves raptor-mtor- and s6k1-dependent serine phosphorylation in cell culture models of tuberous sclerosiss6k1 phosphorylates irs1 in vitro on multiple residues showing strong preference for rxrxxs/t over s/t,p sites.

Identifier	Residue	Sequence	Organism
SIGNOR-127908	Ser307	TRRSRTEsITATSPA	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-148903	Ser527	RFRKRTHsAGTSPTI	Homo sapiens	HEK-293 Cell
pmid	sentence
16914728	Turnover of the active fraction of irs1 involves raptor-mtor- and s6k1-dependent serine phosphorylation in cell culture models of tuberous sclerosiss6k1 phosphorylates irs1 in vitro on multiple residues showing strong preference for rxrxxs/t over s/t,p sites.

Identifier	Residue	Sequence	Organism
SIGNOR-127912	Ser636	SGDYMPMsPKSVSAP	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin.

Identifier	Residue	Sequence	Organism
SIGNOR-127203	Ser639	YMPMSPKsVSAPQQI	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin.

Publications:

6

Organism:

Mus Musculus, Homo Sapiens

Tissue:

Ovary, Myotube, Brain

Pathways:

Insulin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-236022	Ser1101	GCRRRHSsETFSSTP	Homo sapiens
pmid	sentence
17360977	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223

Publications:

1

Organism:

Homo Sapiens

Tissue:

Ovary

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-249267	Ser1101	GCRRRHSsETFSSTP	Cricetulus griseus	CHO Cell
pmid	sentence
15364919	Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).

Identifier	Residue	Sequence	Organism
SIGNOR-124737	Ser616	DDGYMPMsPGVAPVP	Homo sapiens
pmid	sentence
15143153	These results indicate that activation of protein kinase c stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell these data suggest that: 1) activation of pkctheta contributes to ikk and jnk activation by ffas;2) ikk and jnk mediate pkctheta signals for irs-1 serine phosphorylation and degradation; ser-302 phosphorylation is dependent on pi 3-kinase/mtor, whereas ser-307 depends on c-jun nh2-terminal kinase to inhibit irs1 tyrosine phosphorylation. Ser-636 is located around the pi 3-kinase binding site and, therefore, thought to inhibit pi 3-kinase signaling.

Publications:

2

Organism:

Cricetulus Griseus, Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-250907	Ser24	GYLRKPKsMHKRFFV	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-250908	Ser330	SFRVRASsDGEGTMS	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-250909	Ser99	HFAIAADsEAEQDSW	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-250906	Thr502	TPGTGLGtSPALAGD	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-250910	Thr811	ADDSSSStSSDSLGG	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-250911	Thr88	KHLVALYtRDEHFAI	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Publications:

6

Organism:

In Vitro

Identifier	Residue	Sequence	Organism
SIGNOR-135688	Ser24	GYLRKPKsMHKRFFV	Homo sapiens
pmid	sentence
15849359	Phosphorylation of ser24 in the pleckstrin homology domain of insulin receptor substrate-1 by mouse pelle-like kinase/interleukin-1 receptor-associated kinase\| irs-1 mutants s24d or s24e (mimicking phosphorylation at ser(24)) had impaired ability to associate with insulin receptors resulting in diminished tyrosine phosphorylation of irs-1 and impaired ability of irs-1 to bind and activate pi-3 kinase in response to insulin.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-251072	Ser24	GYLRKPKsMHKRFFV	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-251073	Ser330	SFRVRASsDGEGTMS	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-251074	Ser99	HFAIAADsEAEQDSW	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-251077	Thr502	TPGTGLGtSPALAGD	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-251075	Thr811	ADDSSSStSSDSLGG	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Identifier	Residue	Sequence	Organism
SIGNOR-251076	Thr88	KHLVALYtRDEHFAI	in vitro
pmid	sentence
8349691	These data suggest that casein kinase II mediates a portion of the insulin-stimulated serine/threonine phosphorylation of overexpressed IRS-1 in vivo. \| Thr-502 was identified as the major casein kinase II-catalyzed phosphorylation site in rat IRS-1.

Publications:

6

Organism:

In Vitro

Identifier	Residue	Sequence	Organism
SIGNOR-145398	Ser24	GYLRKPKsMHKRFFV	Homo sapiens
pmid	sentence
16574739	We show that pkcalpha is likely to be directly involved in ser24 phosphorylation...These observations are entirely consistent with a recent independent study demonstrating that the IRS1-S24D mutant shows impaired insulin-stimulated IR-IRS-1 interactions, tyrosine phosphorylation of IRS-1, recruitment/activation of PI 3-Kinase, and insulin-stimulated Glut4 translocation

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-251288	Ser268	SDEFRPRsKSQSSSN	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251289	Ser270	EFRPRSKsQSSSNCS	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251290	Ser272	RPRSKSQsSSNCSNP	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251291	Ser274	RSKSQSSsNCSNPIS	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251292	Ser307	TRRSRTEsITATSPA	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251293	Ser312	TESITATsPASMVGG	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251294	Ser341	GTMSRPAsVDGSPVS	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251295	Ser345	RPASVDGsPVSPSTN	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251296	Ser527	RFRKRTHsAGTSPTI	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Identifier	Residue	Sequence	Organism
SIGNOR-251297	Ser531	RTHSAGTsPTITHQK	in vitro
pmid	sentence
12351658	IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.

Publications:

10

Organism:

In Vitro

Identifier	Residue	Sequence	Organism
SIGNOR-277078	Ser307	TRRSRTEsITATSPA	Mus musculus
pmid	sentence
25645159	In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser 307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon HCV infection occurred in a PTEN dependent manner.\|In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser-307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon Hepatitis C virus infection occurred in a PTEN-dependent manner.

Publications:

1

Organism:

Mus Musculus

Pathways:

Insulin Signaling, Luminal Breast Cancer, MTOR Signaling

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106570	Ser307	TRRSRTEsITATSPA	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism
SIGNOR-52700	Ser307	TRRSRTEsITATSPA	Homo sapiens
pmid	sentence
9335553	These results indicate that activation of protein kinase c stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell these data suggest that: 1) activation of pkctheta contributes to ikk and jnk activation by ffas;2) ikk and jnk mediate pkctheta signals for irs-1 serine phosphorylation and degradation; ser-302 phosphorylation is dependent on pi 3-kinase/mtor, whereas ser-307 depends on c-jun nh2-terminal kinase to inhibit irs1 tyrosine phosphorylation. Ser-636 is located around the pi 3-kinase binding site and, therefore, thought to inhibit pi 3-kinase signaling.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106574	Ser312	TESITATsPASMVGG	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106578	Ser315	ITATSPAsMVGGKPG	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism
SIGNOR-106582	Ser616	DDGYMPMsPGVAPVP	Rattus norvegicus
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism
SIGNOR-106586	Ser636	SGDYMPMsPKSVSAP	Rattus norvegicus
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106590	Ser639	YMPMSPKsVSAPQQI	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Publications:

7

Organism:

Rattus Norvegicus, Homo Sapiens

Tissue:

Kidney

Pathways:

Leptin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-236611	Ser307	TRRSRTEsITATSPA	Homo sapiens
pmid	sentence
11160134	Thus, at least three kinases mediate phosphorylation of ser307, including jnk, serine kinases in the pi 3-kinase cascade that are activated byinsulinor igf-1, and mek1-sensitive kinase cascades during tnf-alfa stimulation.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle

Identifier	Residue	Sequence	Organism
SIGNOR-96936	Ser307	TRRSRTEsITATSPA	Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Identifier	Residue	Sequence	Organism
SIGNOR-118857	Ser307	TRRSRTEsITATSPA	Homo sapiens
pmid	sentence
14579029	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Identifier	Residue	Sequence	Organism
SIGNOR-180532	Ser312	TESITATsPASMVGG	Homo sapiens
pmid	sentence
18728222	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Identifier	Residue	Sequence	Organism
SIGNOR-96940	Ser315	ITATSPAsMVGGKPG	Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Identifier	Residue	Sequence	Organism
SIGNOR-118861	Ser315	ITATSPAsMVGGKPG	Homo sapiens
pmid	sentence
14579029	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Publications:

5

Organism:

Homo Sapiens

Tissue:

Muscle, Skeletal Muscle

Identifier	Residue	Sequence	Organism
SIGNOR-244784	Ser307	TRRSRTEsITATSPA	Homo sapiens
pmid	sentence
11160134	Thus, at least three kinases mediate phosphorylation of ser307, including jnk, serine kinases in the pi 3-kinase cascade that are activated byinsulinor igf-1, and mek1-sensitive kinase cascades during tnf-alfa stimulation.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle

Pathways:

Adipogenesis, Insulin Signaling, Luminal Breast Cancer

Identifier	Residue	Sequence	Organism
SIGNOR-118881	Ser307	TRRSRTEsITATSPA	Homo sapiens
pmid	sentence
14579029	Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632

Identifier	Residue	Sequence	Organism
SIGNOR-52696	Ser315	ITATSPAsMVGGKPG	Homo sapiens
pmid	sentence
9335553	These results indicate that activation of protein kinase c stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell these data suggest that: 1) activation of pkctheta contributes to ikk and jnk activation by ffas;2) ikk and jnk mediate pkctheta signals for irs-1 serine phosphorylation and degradation; ser-302 phosphorylation is dependent on pi 3-kinase/mtor, whereas ser-307 depends on c-jun nh2-terminal kinase to inhibit irs1 tyrosine phosphorylation. Ser-636 is located around the pi 3-kinase binding site and, therefore, thought to inhibit pi 3-kinase signaling.

Identifier	Residue	Sequence	Organism
SIGNOR-118873	Tyr612	TLHTDDGyMPMSPGV	Homo sapiens
pmid	sentence
14579029	Map kinases and mtor mediate insulin-induced phosphorylation of insulin receptor substrate-1 on serine residues 307, 612 and 632

Identifier	Residue	Sequence	Organism
SIGNOR-118877	Tyr632	GRKGSGDyMPMSPKS	Homo sapiens
pmid	sentence
14579029	Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632

Publications:

4

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-236760	Ser307	TRRSRTEsITATSPA	Cricetulus griseus
pmid	sentence
15069075	Extensive studies have provided evidence that phosphorylation of Ser307 in IRS-1 inhibits IR/IRS-1 complex formation and IRS-1 tyrosine phosphorylation after prolonged insulin-stimulation similar to our results.

Publications:

1

Organism:

Cricetulus Griseus

Identifier	Residue	Sequence	Organism
SIGNOR-217920	Ser312	TESITATsPASMVGG	Homo sapiens
pmid	sentence
17360977	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase

Publications:

1

Organism:

Homo Sapiens

Tissue:

Ovary

Identifier	Residue	Sequence	Organism
SIGNOR-279520	Ser312	TESITATsPASMVGG	Homo sapiens
pmid	sentence
31723029	DYRK1A interacts with IRS-1 and phosphorylates IRS-1 at Ser-312 and Ser-616.\|We found that DYRK1A overexpression up-regulated IRS-1 expression by slowing the turnover of IRS-1 protein.

Identifier	Residue	Sequence	Organism
SIGNOR-279521	Ser616	DDGYMPMsPGVAPVP	Homo sapiens
pmid	sentence
31723029	DYRK1A interacts with IRS-1 and phosphorylates IRS-1 at Ser-312 and Ser-616.\|We found that DYRK1A overexpression up-regulated IRS-1 expression by slowing the turnover of IRS-1 protein.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-278310	Ser312	TESITATsPASMVGG	Homo sapiens
pmid	sentence
20685959	First, PKR induces phosphorylation of IRS1 at Ser312 and suppresses tyrosine phosphorylation of IRS1, mediated by the insulin receptor substrates kinases, JNK and I\u03baB kinase.\|These results suggest that PKR induces the inhibitory phosphorylation of IRS1 at Ser312 in HepG2 cells, thereby suppressing the phosphorylation at Tyr941.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-152418	Ser312	TESITATsPASMVGG	Homo sapiens	Uveal Melanoma Cell
pmid	sentence
17242212	Our data suggest that il-6 impairs the vasodilator effects of insulin that are mediated by the irs-1/pi3-kinase/akt/enos pathway through activation of jnk and erk1/2.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-235777	Ser312	TESITATsPASMVGG	Rattus norvegicus	H4-II-E-C3 Cell
pmid	sentence
12510059	Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylationOne of the specific Ser phosphorylation sites in IRS-1 that has been proposed to negatively modulate the insulin signal is Ser312 (numbered according to the human sequence). Prior studies have demonstrated that IRS-1 associates with and is phosphorylated by JNK in vitro on Ser312

Publications:

1

Organism:

Rattus Norvegicus

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236591	Ser312	TESITATsPASMVGG	Rattus norvegicus	H4-II-E-C3 Cell
pmid	sentence
12510059	Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylationOne of the specific Ser phosphorylation sites in IRS-1 that has been proposed to negatively modulate the insulin signal is Ser312 (numbered according to the human sequence). Prior studies have demonstrated that IRS-1 associates with and is phosphorylated by JNK in vitro on Ser312

Publications:

1

Organism:

Rattus Norvegicus

Identifier	Residue	Sequence	Organism
SIGNOR-123738	Ser323	MVGGKPGsFRVRASS	Homo sapiens
pmid	sentence
15069075	Thus, pkc-zeta might promote feedback ir/irs-1 complex formation and irs-1 tyrosine phosphorylation through phosphorylation of ser318.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-123734	Ser323	MVGGKPGsFRVRASS	Homo sapiens
pmid	sentence
15069075	Here we show in various cell models that the adipose hormone leptin, a putative mediator in obesity-related insulin resistance, promotes phosphorylation of ser-318 in irs1 by a janus kinase 2, irs2, and pkc-dependent pathway. we observed that insulin stimulates phosphorylation of ser(318) in irs-1, which is mediated, at least partially, by pkc-zeta.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-146105	Ser323	MVGGKPGsFRVRASS	Homo sapiens	Myoblast
pmid	sentence
16611834	Here we show in various cell models that the adipose hormone leptin, a putative mediator in obesity-related insulin resistance, promotes phosphorylation of ser-318 in irs1 by a janus kinase 2, irs2, and pkc-dependent pathway. we observed that insulin stimulates phosphorylation of ser(318) in irs-1, which is mediated, at least partially, by pkc-zeta.

Publications:

2

Organism:

Homo Sapiens

Tissue:

Kidney, Muscle, Skeletal Muscle

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236595	Ser527	RFRKRTHsAGTSPTI	Mus musculus	MEF Cell
pmid	sentence
18498745	In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236599	Ser639	YMPMSPKsVSAPQQI	Mus musculus	MEF Cell
pmid	sentence
18498745	In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8

Publications:

2

Organism:

Mus Musculus

Pathways:

Insulin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-123177	Ser616	DDGYMPMsPGVAPVP	Homo sapiens
pmid	sentence
15001544	Rin beta-cells exposed to high glucose exhibited increased c-jun n-terminal kinase (jnk) and erk1/2 activity, which was associated with increased irs-1 phosphorylation at serine (ser)(307) and ser(612), respectively, that inhibits coupling of irs-1 to the insulin receptor and is upstream of the inhibition of irs-1 tyrosine phosphorylation.

Identifier	Residue	Sequence	Organism
SIGNOR-249409	Ser636	SGDYMPMsPKSVSAP	Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-96944	Ser616	DDGYMPMsPGVAPVP	Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Identifier	Residue	Sequence	Organism
SIGNOR-96948	Ser636	SGDYMPMsPKSVSAP	Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-123173	Ser616	DDGYMPMsPGVAPVP	Homo sapiens
pmid	sentence
15001544	Rin beta-cells exposed to high glucose exhibited increased c-jun n-terminal kinase (jnk) and erk1/2 activity, which was associated with increased irs-1 phosphorylation at serine (ser)(307) and ser(612), respectively, that inhibits coupling of irs-1 to the insulin receptor and is upstream of the inhibition of irs-1 tyrosine phosphorylation.

Identifier	Residue	Sequence	Organism
SIGNOR-249407	Ser636	SGDYMPMsPKSVSAP	Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-99055	Ser794	QHLRLSTsSGRLLYA	Homo sapiens
pmid	sentence
12624099	These results suggest that highly expressed sik2 in insulin-stimulated adipocytes phosphorylates ser794_ of irs-1 and, as a result, might modulate the efficiency ofinsulinsignal transduction

Identifier	Residue	Sequence	Organism
SIGNOR-99059	Ser794	QHLRLSTsSGRLLYA	Homo sapiens
pmid	sentence
12624099	Sik2 could phosphorylate ser(794) of human irs-1

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence
SIGNOR-265745	Ser794	QHLRLSTsSGRLLYA
pmid	sentence
24841198	SIK2 is known to attenuate insulin signaling by phosphorylating IRS-1/Ser789

Publications:

1

Identifier	Residue	Sequence	Organism
SIGNOR-157730	Tyr1179	GLENGLNyIDLDLVK	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Sequence	Organism
SIGNOR-157734	Tyr1229	SSEDLSAyASISFQK	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Sequence	Organism
SIGNOR-157738	Tyr465	GEEELSNyICMGGKG	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Sequence	Organism
SIGNOR-157742	Tyr612	TLHTDDGyMPMSPGV	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Sequence	Organism
SIGNOR-157746	Tyr632	GRKGSGDyMPMSPKS	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Sequence	Organism
SIGNOR-157750	Tyr896	EPKSPGEyVNIEFGS	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Sequence	Organism
SIGNOR-157754	Tyr941	EETGTEEyMKMDLGP	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Sequence	Organism
SIGNOR-157758	Tyr989	VPSSRGDyMTMQMSC	Homo sapiens
pmid	sentence
17827393	Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K).

Identifier	Residue	Organism
SIGNOR-255104		Homo sapiens
pmid	sentence
15829723	IGF-I binding to its receptor activates the kinase activity of the receptor, which then recruits the insulin response substrate-1, causing activation of phosphatidyl-inositol-3 kinase (PI3K) to phosphorylate Akt.

Identifier	Residue	Organism
SIGNOR-175665		Homo sapiens
pmid	sentence
21798082	Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor.

Publications:

10

Organism:

Homo Sapiens

Tissue:

Skeletal Muscle

Pathways:

IGF and Myogenesis

Identifier	Residue	Sequence	Organism
SIGNOR-74856	Tyr1179	GLENGLNyIDLDLVK	Homo sapiens
pmid	sentence
10660596	The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1b (ptp1b), sh2 domain-containing ptpase-2 (shp-2), leukocyte common antigen-related (lar), and leukocyte antigen-related phosphatase) (lrp) toward irs-1 dephosphorylation was studied using recombinant proteins in vitro. Ptp1b exhibited the highest specific activity these results provide new insight into novel molecular interactions involving ptp1b and grb2 that may influence the steady-state capacity of irs-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling.

Identifier	Residue	Sequence	Organism
SIGNOR-27024	Tyr1179	GLENGLNyIDLDLVK	Homo sapiens
pmid	sentence
7515062	The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1b (ptp1b), sh2 domain-containing ptpase-2 (shp-2), leukocyte common antigen-related (lar), and leukocyte antigen-related phosphatase) (lrp) toward irs-1 dephosphorylation was studied using recombinant proteins in vitro. Ptp1b exhibited the highest specific activity these results provide new insight into novel molecular interactions involving ptp1b and grb2 that may influence the steady-state capacity of irs-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling.

Identifier	Residue	Sequence	Organism
SIGNOR-27028	Tyr896	EPKSPGEyVNIEFGS	Homo sapiens
pmid	sentence
7515062	The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1b (ptp1b), sh2 domain-containing ptpase-2 (shp-2), leukocyte common antigen-related (lar), and leukocyte antigen-related phosphatase) (lrp) toward irs-1 dephosphorylation was studied using recombinant proteins in vitro. Ptp1b exhibited the highest specific activity these results provide new insight into novel molecular interactions involving ptp1b and grb2 that may influence the steady-state capacity of irs-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling.

Identifier	Residue	Sequence	Organism
SIGNOR-74860	Tyr896	EPKSPGEyVNIEFGS	Homo sapiens
pmid	sentence
10660596	The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1b (ptp1b), sh2 domain-containing ptpase-2 (shp-2), leukocyte common antigen-related (lar), and leukocyte antigen-related phosphatase) (lrp) toward irs-1 dephosphorylation was studied using recombinant proteins in vitro. Ptp1b exhibited the highest specific activity these results provide new insight into novel molecular interactions involving ptp1b and grb2 that may influence the steady-state capacity of irs-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling.

Publications:

4

Organism:

Homo Sapiens

Pathways:

Leptin Signaling

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236752	Tyr1229	SSEDLSAyASISFQK	Cricetulus griseus	CHO Cell
pmid	sentence
7651388	Therefore, during insulin stimulation irs-1 undergoes tyrosine phosphorylation, and a portion of tyrosine phosphorylated irs-1 associated with the insulin receptor. The insulin receptor substrate-1 (irs-1) is rapidly phosphorylated on several tyrosine residues by the activated insulin receptor. Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (irs-1) and shc by the activated insulin receptor (ir).

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-235983	Tyr1229	SSEDLSAyASISFQK	Homo sapiens	Adipocyte
pmid	sentence
12220227	Here we show that stimulation by insulin of freshly isolated primary adipocytes resulted in the expected rapid tyrosine phosphorylation of the insulin receptor, IRS-1 and IRS-3. Inhibition of PI 3-kinase enhanced the insulin-stimulated phosphorylation of IRS-1 on (i) Tyr(612) and Tyr(941) (p85 binding sites), concomitant with an increased association of the p85 subunit of PI 3-kinase; (ii) Tyr(896) (a Grb2 binding site); and (iii) Tyr(1229) (an SHP-2 binding site), although little or no binding of SHP-2 to IRS-1 was detectable under any conditions.

Identifier	Residue	Sequence	Organism
SIGNOR-236713	Tyr465	GEEELSNyICMGGKG	Rattus norvegicus
pmid	sentence
7651388	All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin receptors A previous study using phosphopeptides suggested that tyrosine-phosphorylated YXXM motifs at positions 608 and 939 in rat IRS-1 bind with high affinity to SH2 domains of p85, and motifs at positions 460 and 987 bind with lower affinity (10).

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236756	Tyr612	TLHTDDGyMPMSPGV	Cricetulus griseus	CHO Cell
pmid	sentence
7651388	Therefore, during insulin stimulation irs-1 undergoes tyrosine phosphorylation, and a portion of tyrosine phosphorylated irs-1 associated with the insulin receptor. The insulin receptor substrate-1 (irs-1) is rapidly phosphorylated on several tyrosine residues by the activated insulin receptor. Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (irs-1) and shc by the activated insulin receptor (ir).

Identifier	Residue	Sequence	Organism
SIGNOR-235971	Tyr612	TLHTDDGyMPMSPGV	Rattus norvegicus
pmid	sentence
11416002	All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin re- ceptors Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236741	Tyr632	GRKGSGDyMPMSPKS	Cricetulus griseus	CHO Cell
pmid	sentence
7651388	Therefore, during insulin stimulation irs-1 undergoes tyrosine phosphorylation, and a portion of tyrosine phosphorylated irs-1 associated with the insulin receptor. The insulin receptor substrate-1 (irs-1) is rapidly phosphorylated on several tyrosine residues by the activated insulin receptor. Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (irs-1) and shc by the activated insulin receptor (ir).

Identifier	Residue	Sequence	Organism
SIGNOR-236709	Tyr632	GRKGSGDyMPMSPKS	Rattus norvegicus
pmid	sentence
11416002	All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin re- ceptors Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells

Identifier	Residue	Sequence	Organism
SIGNOR-236725	Tyr896	EPKSPGEyVNIEFGS	Homo sapiens
pmid	sentence
12220227	Here we show that stimulation by insulin of freshly isolated primary adipocytes resulted in the expected rapid tyrosine phosphorylation of the insulin receptor, IRS-1 and IRS-3. Inhibition of PI 3-kinase enhanced the insulin-stimulated phosphorylation of IRS-1 on (i) Tyr(612) and Tyr(941) (p85 binding sites), concomitant with an increased association of the p85 subunit of PI 3-kinase; (ii) Tyr(896) (a Grb2 binding site); and (iii) Tyr(1229) (an SHP-2 binding site), although little or no binding of SHP-2 to IRS-1 was detectable under any conditions.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236745	Tyr896	EPKSPGEyVNIEFGS	Cricetulus griseus	CHO Cell
pmid	sentence
7651388	Therefore, during insulin stimulation irs-1 undergoes tyrosine phosphorylation, and a portion of tyrosine phosphorylated irs-1 associated with the insulin receptor. The insulin receptor substrate-1 (irs-1) is rapidly phosphorylated on several tyrosine residues by the activated insulin receptor. Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (irs-1) and shc by the activated insulin receptor (ir).

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-235975	Tyr941	EETGTEEyMKMDLGP	Rattus norvegicus	Adipocyte
pmid	sentence
7651388	All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin receptors A previous study using phosphopeptides suggested that tyrosine-phosphorylated YXXM motifs at positions 608 and 939 in rat IRS-1 bind with high affinity to SH2 domains of p85, and motifs at positions 460 and 987 bind with lower affinity (10).

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-235979	Tyr989	VPSSRGDyMTMQMSC	Rattus norvegicus	Adipocyte
pmid	sentence
7651388	All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin receptors A previous study using phosphopeptides suggested that tyrosine-phosphorylated YXXM motifs at positions 608 and 939 in rat IRS-1 bind with high affinity to SH2 domains of p85, and motifs at positions 460 and 987 bind with lower affinity (10).

Publications:

11

Organism:

Cricetulus Griseus, Homo Sapiens, Rattus Norvegicus

Pathways:

Adipogenesis, AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, Leptin Signaling, mTOR in cancer, MTOR Signaling

Identifier	Residue	Organism	Cell Line
SIGNOR-100768		Homo sapiens	T-lymphocyte, Macrophage, Monocyte
pmid	sentence
12704343	Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle, Lung, Smooth Muscle

Identifier	Residue	Organism
SIGNOR-74852		in vitro
pmid	sentence
10660596	Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein.

Publications:

1

Organism:

In Vitro

Pathways:

Insulin Signaling

Identifier	Residue	Organism
SIGNOR-144159		Homo sapiens
pmid	sentence
16452206	The mtor inhibitory drug rapamycin up-regulates irs-1 protein levels and induces akt phosphorylation, protein kinase activity, and downstream signaling.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-252694		Rattus norvegicus
pmid	sentence
21798082	Phosphorylated irs then acts as docking site to recruit and activate phosphatidylinositol-3-kinase (pi3k) which phosphorylates membrane phospholipids, generating phosphoinositide-3,4,5-triphosphate (pip3) from phosphoinositide-4,5-biphosphate (pip2).

Identifier	Residue	Organism
SIGNOR-252695		Homo sapiens
pmid	sentence
20966354	Irs proteins are capable of both regulating and activating pi3k, depending on the cell of origin.

Identifier	Residue	Organism
SIGNOR-256170		Homo sapiens
pmid	sentence
20966354	Irs proteins are capable of both regulating and activating pi3k, depending on the cell of origin.

Publications:

3

Organism:

Rattus Norvegicus, Homo Sapiens

Tissue:

Skeletal Muscle, Lung Cancer Cell

Pathways:

Leptin Signaling, mTOR in cancer

Identifier	Residue	Organism
SIGNOR-277053		Homo sapiens
pmid	sentence
17638892	Finally, we report that PTPL1 expression is sufficient to block the IRS-1/phosphatidylinositol 3-kinase/Akt signaling pathway, to inhibit the insulin-like growth factor-I effect on cell survival, and to induce apoptosis.\|We first show by complementary approaches that PTPL1 specifically dephosphorylates insulin receptor substrate-1 (IRS-1) in vitro and in cellulo.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-270132		Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Adipogenesis, AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, Leptin Signaling, MTOR Signaling

Identifier	Residue	Organism
SIGNOR-175687		Homo sapiens
pmid	sentence
21798082	Negative feedback involves s6k, which inactivates irs by phosphorylation at multiple sites, thus inducing its degradation and altered cell localization.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Skeletal Muscle

Pathways:

AMPK Signaling, MTOR Signaling

Identifier	Residue	Organism	Cell Line
SIGNOR-265757		Homo sapiens	Hep-G2 Cell
pmid	sentence
23720771	In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells\|Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation\|Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-236737		Homo sapiens
pmid	sentence
17360977	Research has focused on insulin receptor substrate (IRS)-1 as a locus for insulin resistance. Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal. Insulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223

Publications:

1

Organism:

Homo Sapiens

Pathways:

Adipogenesis, AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, Leptin Signaling, mTOR in cancer, MTOR Signaling

Identifier	Residue	Organism
SIGNOR-279183		Homo sapiens
pmid	sentence
20466847	HG activates GSK3beta, which phosphorylates IRS1 at serine 332, leading to the ubiquitination and proteasome mediated degradation of IRS1.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Adipogenesis, Insulin Signaling, MTOR Signaling, IGF and Myogenesis

Identifier	Residue	Organism	Cell Line
SIGNOR-235487		Mus musculus	NIH-3T3 Cell
pmid	sentence
11416002	To examine contributions of specific YXXM motifs in human insulin receptor substrate-1 (IRS-1) to mediating the metabolic actions of insulin, we studied IRS-1 mutants containing various substitutions of Phe for Tyr. In transfected NIH-3T3(IR) cells, insulin stimulation caused a 5-fold increase in phosphatidylinositol 3-kinase (PI3K) activity coimmunoprecipitated with wild-type IRS-1

Identifier	Residue	Organism
SIGNOR-236618		Mus musculus
pmid	sentence
14623899	As shown previously, IRS-1 was required for insulin-stimulated phosphorylation of Akt in 32D cells, which is consistent with the binding and activation of PI3K by IRS-1 during insulin stimulation

Publications:

2

Organism:

Mus Musculus

Tissue:

Muscle

Pathways:

Adipogenesis, Insulin Signaling

Identifier	Residue	Organism
SIGNOR-106599		Homo sapiens
pmid	sentence
11287630	Irs-1 tyrosine phosphorylation by tnf was blocked by rapamycin, an inhibitor of the mammalian target of rapamycin (mtor), a downstream target of akt. these results suggest that tnf impairs insulin signaling through irs-1

Publications:

1

Organism:

Homo Sapiens

Pathways:

MTOR Signaling

Identifier	Residue	Organism
SIGNOR-175668		Rattus norvegicus
pmid	sentence
21798082	Phosphorylated irs then acts as docking site to recruit and activate phosphatidylinositol-3-kinase (pi3k) which phosphorylates membrane phospholipids, generating phosphoinositide-3,4,5-triphosphate (pip3) from phosphoinositide-4,5-biphosphate (pip2).

Publications:

1

Organism:

Rattus Norvegicus

Tissue:

Skeletal Muscle

Pathways:

MTOR Signaling, IGF and Myogenesis

Identifier	Residue	Organism
SIGNOR-168985		Homo sapiens
pmid	sentence
20966354	Irs proteins are capable of both regulating and activating pi3k, depending on the cell of origin.

Publications:

1

Organism:

Homo Sapiens

Pathways:

AMPK Signaling, Luminal Breast Cancer, mTOR in cancer, MTOR Signaling, IGF and Myogenesis

Identifier	Residue	Organism	Cell Line
SIGNOR-236614		Homo sapiens	Brown Adipose Tissue
pmid	sentence
11259577	Association ofinsulinreceptor substrate 1 (irs-1) y895 with grb-2 mediates theinsulinsignaling involved in irs-1-deficient brown adipocyte mitogenesis.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Adipogenesis, Insulin Signaling, Luminal Breast Cancer

Identifier	Residue	Organism	Cell Line
SIGNOR-251343		Mus musculus	32D Cell
pmid	sentence
9305869	Janus kinase-dependent activation of insulin receptor substrate 1

Publications:

1

Organism:

Mus Musculus

Identifier	Residue	Organism
SIGNOR-52707		Homo sapiens
pmid	sentence
9335553	These results indicate that activation of protein kinase c stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell these data suggest that: 1) activation of pkctheta contributes to ikk and jnk activation by ffas;2) ikk and jnk mediate pkctheta signals for irs-1 serine phosphorylation and degradation; ser-302 phosphorylation is dependent on pi 3-kinase/mtor, whereas ser-307 depends on c-jun nh2-terminal kinase to inhibit irs1 tyrosine phosphorylation. Ser-636 is located around the pi 3-kinase binding site and, therefore, thought to inhibit pi 3-kinase signaling.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Kidney

Identifier	Residue	Organism
SIGNOR-199361		Homo sapiens
pmid	sentence
23115649	Irs-1 is the major signaling protein that socs3 targets to inhibit insulin signaling

Publications:

1

Organism:

Homo Sapiens

Pathways:

Leptin Signaling

Identifier	Residue	Organism
SIGNOR-104911		Homo sapiens
pmid	sentence
11160134	Ly294002 or wortmannin were used to determine whether pi 3-kinasedependent pathways mediate ser307 phosphorylation during insulin/igf-1 or TNF-alpha Stimulation. As expected, the pi-3 kinase inhibitors ly294002 or wortmannin inhibited activation of pkb/akt in insulin or igf-1 stimulated 3t3-l1 preadipocytes, but were without effect on erk1/2. these results suggest that elements of the pi 3-kinase cascade mediate insulin/igf-1stimulated phosphorylation of ser307

Publications:

1

Organism:

Homo Sapiens

Pathways:

AMPK Signaling, Luminal Breast Cancer, mTOR in cancer, MTOR Signaling, IGF and Myogenesis

Identifier	Residue	Organism	Cell Line
SIGNOR-266962		Chlorocebus aethiops	COS-1 Cell
pmid	sentence
12242307	We have recently reported the isolation of a PH domain-interacting protein, PHIP, which selectively binds to the IRS-1 PH domain and is stably associated with IRS-1 in mammalian cells. Here we demonstrate that overexpression of PHIP in fibroblasts enhances insulin-induced transcriptional responses in a mitogen-activated protein kinase-dependent manner.

Publications:

1

Organism:

Chlorocebus Aethiops

Identifier	Residue	Organism
SIGNOR-271941		Mus musculus
pmid	sentence
23142081	We provide evidence that mTORC2 can stabilize Fbw8, the substrate-targeting subunit of the CUL7 E3 ligase complex that has been shown to mediate degradation of IRS-1 .

Publications:

1

Organism:

Mus Musculus

Identifier	Residue	Organism
SIGNOR-278520		Homo sapiens
pmid	sentence
23965929	Here, we demonstrate that MG53 induces IRS-1 ubiquitination with the help of the E2 enzyme UBE2H during skeletal myogenesis by examining MG53 disrupted skeletal muscle cells and tissues.\|The IRS-1 protein level was decreased by MG53 in a concentration dependent manner and was restored by the addition of MG132, a proteasome inhibitor (XREF_FIG; XREF_SUPPLEMENTARY).

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-265756		Homo sapiens	Hep-G2 Cell
pmid	sentence
23720771	In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells\|Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation\|Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-269997		Homo sapiens
pmid	sentence
12510059	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-49531		Homo sapiens	Neuron
pmid	sentence
9223670	Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-271939		Mus musculus	MEF Cell
pmid	sentence
23142081	Defective IRS-1 degradation was due to attenuated expression and phosphorylation of the ubiquitin ligase substrate-targeting subunit, Fbw8. mTORC2 stabilizes Fbw8 by phosphorylation at Ser86, allowing the insulin-induced translocation of Fbw8 to the cytosol where it mediates IRS-1 degradation.

Publications:

1

Organism:

Mus Musculus

Identifier	Residue	Organism
SIGNOR-252787		Homo sapiens
pmid	sentence
21798082	Negative feedback involves s6k, which inactivates irs by phosphorylation at multiple sites, thus inducing its degradation and altered cell localization.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Skeletal Muscle

Pathways:

Leptin Signaling

Identifier	Residue	Organism
SIGNOR-236625		Rattus norvegicus
pmid	sentence
15069075	The mechanism by which the phosphorylation of ser307 or ser318 inhibits irs-1 tyrosine phosphorylation is not known. Prolonged insulin-stimulation inhibits irs-1 binding to the phosphorylated npey motif in the juxta-membrane region of the irbeta -subunit.

Publications:

1

Organism:

Rattus Norvegicus

Pathways:

Adipogenesis, AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, Leptin Signaling, mTOR in cancer, MTOR Signaling

Identifier	Residue	Organism
SIGNOR-252717		Homo sapiens
pmid	sentence
11160134	Ly294002 or wortmannin were used to determine whether pi 3-kinasedependent pathways mediate ser307 phosphorylation during insulin/igf-1 or TNF-alpha Stimulation. As expected, the pi-3 kinase inhibitors ly294002 or wortmannin inhibited activation of pkb/akt in insulin or igf-1 stimulated 3t3-l1 preadipocytes, but were without effect on erk1/2. these results suggest that elements of the pi 3-kinase cascade mediate insulin/igf-1stimulated phosphorylation of ser307

Publications:

1

Organism:

Homo Sapiens

Pathways:

Leptin Signaling, mTOR in cancer

Name	IRS1 View Modifications
Full Name	Insulin receptor substrate 1
Synonyms	IRS-1
Primary ID	P35568
Links	- -
Type	protein
Relations	135
Pathways	Adipogenesis, AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, Leptin Signaling, mTOR in cancer, MTOR Signaling, Myofiber: IGF1R, Satellite: IGF1, Satellite: IGF1R, Satellite: miRNA network
Function	May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).

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