| + |
MEK1/2 | down-regulates 
phosphorylation
|
TAL1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244975 |
Ser122 |
DGRMVQLsPPALAAP |
Homo sapiens |
|
| pmid |
sentence |
| 11904294 |
We found that hypoxia greatly accelerated tal1 turnover in these cells through mitogen-activated protein kinase (mapk)2-mediated phosphorylation, ubiquitination, and proteasomal degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MEK1/2 | down-regulates
phosphorylation
|
IRS1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| 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 |
| + |
MEK1/2 | down-regulates quantity by destabilization
phosphorylation
|
TIAM1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276674 |
Ser329 |
DVNAGEGsEFADSGI |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 25124033 |
Phosphorylation of Ser329, Ser334, and Thr340 in Tiam1 is required for its interaction with βTrCP1. The proteolysis of Tiam1 is prevented by βTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MEK1/2 | up-regulates activity 
phosphorylation
|
MAPK1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244792 |
Thr185 |
HDHTGFLtEYVATRW |
Homo sapiens |
BJ Cell |
| pmid |
sentence |
| 11971971 |
Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244788 |
Tyr187 |
HTGFLTEyVATRWYR |
Homo sapiens |
BJ Cell |
| pmid |
sentence |
| 11971971 |
Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244795 |
|
|
Homo sapiens |
Adipocyte |
| pmid |
sentence |
| 12270934 |
Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258990 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 11730323 |
Raf proteins have been shown to phosphorylate and activate MAPKKs (MAP kinase kinases) called MEKs (MAPK or ERK kinases) which in turn phosphorylate and activate MAPKs (MAP kinases) called ERKs |
|
| Publications: |
4 |
Organism: |
Homo Sapiens, Mus Musculus |
| + |
MEK1/2 | up-regulates
phosphorylation
|
MAPK3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244802 |
Thr202 |
HDHTGFLtEYVATRW |
Homo sapiens |
|
| pmid |
sentence |
| 9677429 |
The mek1 proline-rich insert is required for efficient activation of the mitogen-activated protein kinases erk1 and erk2 in mammalian cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244806 |
Tyr204 |
HTGFLTEyVATRWYR |
Homo sapiens |
|
| pmid |
sentence |
| 9677429 |
The mek1 proline-rich insert is required for efficient activation of the mitogen-activated protein kinases erk1 and erk2 in mammalian cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244798 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12270934 |
Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
MEK1/2 | up-regulates activity
phosphorylation
|
GSK3B |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244780 |
Tyr216 |
RGEPNVSyICSRYYR |
Homo sapiens |
|
| pmid |
sentence |
| 15020233 |
In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, AML_TRIPLETS, FLT3-ITD signaling, Insulin Signaling, PI3K/AKT Signaling |
| + |
PAK | up-regulates
phosphorylation
|
MEK1/2 |
0.564 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244920 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 16129686 |
Inhibition of pak kinase activity dramatically decreased phosphorylation of mek1 at ser(298) in response to either pdgf or egf. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PDPK1 | up-regulates activity
phosphorylation
|
MEK1/2 |
0.275 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244934 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15175348 |
In vitro kinase assay revealed that the direct targets of pdk1 in the mapk pathway were the upstream mapk kinases mek1 and mek2. The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, B-cell activation, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, Insulin Signaling, Luminal Breast Cancer, Malignant Melanoma, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
LAMTOR3 | up-regulates
binding
|
MEK1/2 |
0.6 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244874 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15547943 |
We analyzed the ability of mp1 to bind to mek1, erk1, and to itself, and the regulation of these interactions. Gel filtration of cell lysates revealed two major mp1 peaks: a broad high molecular weight peak and a 28 kda complex. An mp1 mutant that lost mek1 binding no longer enhanced rasv12-stimulated erk1 activity, and functioned as a dominant negative, consistent with the concept that mp1 function depends on facilitating these oligomerizations. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
2-(2-amino-3-methoxyphenyl)chromen-4-one | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244930 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 11160424 |
The mek1/2 inhibitors pd98059, sl327, and u0126 have been extensively used to implicate erk1/2 in neuroplasticity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
MAPK14 | down-regulates activity 
|
MEK1/2 |
0.659 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263511 |
|
|
Homo sapiens |
Skin Fibroblast |
| pmid |
sentence |
| 12839928 |
Activation of p38 MAPK is required for arsenite-induced apoptosis and MEK1,2 dephosphorylation in human skin fibroblasts. Our data suggest the presence of a continuous negative feedback from p38α and p38β to MEK1,2 as simultaneous inhibition of p38α and p38β isoforms in normal quiescent cells resulted in accumulation of phosphorylated MEK1,2 (Fig. 2A) ⇓ . This negative regulation of MEK1,2 in normal cells could be considered a means to control MEK1,2-mediated proliferation and expression of transformation-related genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Toll like receptors |
| + |
PPP2CA | down-regulates
dephosphorylation
|
MEK1/2 |
0.54 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244941 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20626350 |
In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, PI3K/AKT Signaling |
| + |
MEK1/2 | up-regulates
phosphorylation
|
ERK1/2 |
0.747 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244776 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11971971 |
Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling |
| + |
FGFR1 | up-regulates 
|
MEK1/2 |
0.315 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244865 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12270934 |
Fibroblast growth factor-2 (FGF-2), in the presence of dexamethasone, isobutylmethylxanthine, and insulin, induces a prolonged activation of the MEK/ERK signaling pathway, which lasts for at least 12 h post-induction, and this activity is less sensitive to the MEK inhibitors |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Luminal Breast Cancer |
| + |
MAP3K2 | up-regulates
phosphorylation
|
MEK1/2 |
0.424 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244888 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11343802 |
Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK1 | down-regulates activity
phosphorylation
|
MEK1/2 |
0.743 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244912 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 10567369 |
An ERK2-binding site at the N terminus of MEK1 was reported to mediate their stable association. We examined the importance of this binding site in the feedback phosphorylation of mek1 on thr(292) and thr(386) by erk2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244916 |
|
|
Chlorocebus aethiops |
COS Cell |
| pmid |
sentence |
| 14993270 |
We propose that activation of erk during adhesion creates a feedback system in which erk phosphorylates mek1 on t292, and this in turn blocks additional s298 phosphorylation in response to integrin signaling. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Chlorocebus Aethiops |
| + |
trametinib | down-regulates activity
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259446 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26347206 |
Trametinib (Mekinist™) is a reversible and highly selective allosteric inhibitor of MEK1 and MEK2 with anticancer activity against metastatic melanoma carrying the BRAF V600 mutation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262312 |
|
|
Homo sapiens |
HuH-7 Cell |
| pmid |
sentence |
| 25487801 |
Inhibitors of MEK1/2 (trametinib) and/or ERK1/2 (selumetinib) had the strongest and most conserved inhibitory activities, suggesting that MEK1/2 and ERK1/2 may have unique capabilities as stand-alone or combinatorial therapies for MERS-CoV infections. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV MAPK PERTURBATION |
| + |
selumetinib | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244823 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV MAPK PERTURBATION |
| + |
BRAF | up-regulates activity
phosphorylation
|
MEK1/2 |
0.779 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244831 |
|
|
in vitro |
|
| pmid |
sentence |
| 8413257 |
Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251988 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21900390 |
BRAFV600E has been shown to initiate thyroid follicular cell transformation. The BRAFV600E mutation disrupts the hydrophobic interaction, enabling the BRAF kinase to fold into a catalytically active formation, resulting in an almost 500-fold increase in kinase activity. Mutant BRAF can dimerize and activate MEK without Ras activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244827 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 8131746 |
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf. |
|
| Publications: |
3 |
Organism: |
In Vitro, Homo Sapiens, Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
FGFR2 | up-regulates
|
MEK1/2 |
0.307 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244868 |
|
|
Mus musculus |
3T3-L1 Cell |
| pmid |
sentence |
| 12270934 |
Fibroblast growth factor-2 (FGF-2), in the presence of dexamethasone, isobutylmethylxanthine, and insulin, induces a prolonged activation of the MEK/ERK signaling pathway, which lasts for at least 12 h post-induction, and this activity is less sensitive to the MEK inhibitors |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ARAF | up-regulates
phosphorylation
|
MEK1/2 |
0.742 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244809 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21779497 |
Active raf phosphorylates mek. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244813 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 8621729 |
Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | EGFR Signaling |
| + |
MEK1/2 | up-regulates quantity by expression
transcriptional regulation
|
CHEK1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263069 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28138032 |
Mechanistically, Ras-MEK signaling drives Chk1 expression and promotes cancer cell growth that produces genotoxic stress that requires Chk1 to mediate a response to the consequent DNA damage. Reciprocally, Chk1 engages a negative feedback loop to prevent hyperactivation of Ras-MEK signaling, thereby limiting DNA damage. Ras–MEK signaling transcriptionally activates Chk1, which appears to sustain cancer cell growth by maintaining DNA damage levels below a threshold that would otherwise drive apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
PDPK1 | up-regulates
phosphorylation
|
MEK1/2 |
0.275 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244938 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15175348 |
The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, B-cell activation, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, Insulin Signaling, Luminal Breast Cancer, Malignant Melanoma, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
RAF1 | up-regulates
phosphorylation
|
MEK1/2 |
0.737 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244952 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11018021 |
The best characterized Raf substrates are MEK1 and MEK2. The activation of MEK1/2 by Raf is required to mediate many of the cellular responses to Raf activation, suggesting that MEK1/2 are the dominant Raf effector proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
ERK1/2 | down-regulates activity
phosphorylation
|
MEK1/2 |
0.747 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244858 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 10567369 |
An ERK2-binding site at the N terminus of MEK1 was reported to mediate their stable association. We examined the importance of this binding site in the feedback phosphorylation of mek1 on thr(292) and thr(386) by erk2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244862 |
|
|
Chlorocebus aethiops |
COS Cell |
| pmid |
sentence |
| 14993270 |
We propose that activation of erk during adhesion creates a feedback system in which erk phosphorylates mek1 on t292, and this in turn blocks additional s298 phosphorylation in response to integrin signaling. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Chlorocebus Aethiops |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling |
| + |
MEK1/2 | up-regulates
phosphorylation
|
Gbeta |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269913 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12270934 |
Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PAK1 | up-regulates activity
phosphorylation
|
MEK1/2 |
0.563 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244924 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12876277 |
We find that adhesion to fibronectin induces pak1-dependent phosphorylation of mek1 on s298 and that this phosphorylation is necessary for efficient activation of mek1 and subsequent mapk activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EGFR Signaling, T cell activation, Toll like receptors |
| + |
SL-327 | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244955 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 11160424 |
The mek1/2 inhibitors pd98059, sl327, and u0126 have been extensively used to implicate erk1/2 in neuroplasticity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
MAPK11 | down-regulates activity
|
MEK1/2 |
0.457 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263512 |
|
|
Homo sapiens |
Skin Fibroblast |
| pmid |
sentence |
| 12839928 |
Activation of p38 MAPK is required for arsenite-induced apoptosis and MEK1,2 dephosphorylation in human skin fibroblasts. Our data suggest the presence of a continuous negative feedback from p38α and p38β to MEK1,2 as simultaneous inhibition of p38α and p38β isoforms in normal quiescent cells resulted in accumulation of phosphorylated MEK1,2 (Fig. 2A) ⇓ . This negative regulation of MEK1,2 in normal cells could be considered a means to control MEK1,2-mediated proliferation and expression of transformation-related genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)-4-pyridinecarboxamide | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244820 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
U0126 | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244958 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9873633 |
The mek1/2 inhibitors pd98059, sl327, and u0126 have been extensively used to implicate erk1/2 in neuroplasticity. u0126 was found to functionally antagonize ap-1 transcriptional activity via noncompetitive the dual specificity kinase mek with an ic50 of 0.07 microm for mek 1 and 0.06 microm for mek 2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
U0126.EtOH | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244961 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MEK1/2 | down-regulates
|
MEK1/2 |
0.618 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244877 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18481201 |
Pd98059, a specific inhibitor of mek in addition, immunoblot and immunostaining analysis revealed that phosphorylation of erk was increased by treatment with sb203580;whereas pd98059 increased the phosphorylation of p38, which implies a seesaw-like balance between erk and p38 phosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling |
| + |
MAP3K1 | up-regulates activity
phosphorylation
|
MEK1/2 |
0.645 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244881 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 8131746 |
Phosphorylation at ser-218 and ser-222 by map kinase kinase kinases (raf or mekk1) positively regulates mek1 kinase activity. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | COVID-19 Causal Network, EGFR Signaling, SARS-CoV MAPK PERTURBATION, Toll like receptors |
| + |
MEK1/2 | up-regulates quantity by expression
transcriptional regulation
|
CEBPA |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244773 |
|
|
Mus musculus |
3T3-L1 Cell |
| pmid |
sentence |
| 12270934 |
We further show that activation of mek1 significantly enhances the transactivation of the c/ebpalpha minimal promoter during the early phase of the differentiation process. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, FLT3 in AML, AML_TRIPLETS, NPM1_new |
| + |
ANXA3 | up-regulates activity
|
MEK1/2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262210 |
|
|
Homo sapiens |
A-549 Cell |
| pmid |
sentence |
| 27995049 |
We also investigated the potential regulation of cancer-associated signaling pathways by Anxa3 through screening for the altered expression of some common signaling molecules after Anxa3 downregulation. Decreased phosphorylation of MEK1/2, ERK1/2, Akt, and IκBα was detected after downregulating Anxa3 expression in A549 cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK1 | down-regulates
phosphorylation
|
MEK1/2 |
0.473 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244847 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8114697 |
P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, KIT in AML |
| + |
MAP3K8 | up-regulates
phosphorylation
|
MEK1/2 |
0.556 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244904 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15466476 |
Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244892 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8131746 |
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Toll like receptors |
| + |
WDR83 | up-regulates
binding
|
MEK1/2 |
0.512 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244964 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15118098 |
Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
trametinib | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244871 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV MAPK PERTURBATION |
| + |
PD318088 | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244927 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MEK1/2 | up-regulates activity
phosphorylation
|
ERK1/2 |
0.747 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258989 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 11730323 |
Raf proteins have been shown to phosphorylate and activate MAPKKs (MAP kinase kinases) called MEKs (MAPK or ERK kinases) which in turn phosphorylate and activate MAPKs (MAP kinases) called ERKs |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling |
| + |
PDCD1 | down-regulates activity
|
MEK1/2 |
0.268 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275410 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 22740686 |
MEK1/2 was phosphorylated and activated upon activation of T cells through TCR-CD3 and CD28, which resulted in phosphorylation of its downstream target ERK1/2, as determined by Western blotting analysis with an antibody specific for ERK1/2 phosphorylated at Thr202 and Tyr204, markers of activation. PD-1 substantially inhibited the activation of MEK1/2 and ERK1/2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MEK1/2 | up-regulates activity
phosphorylation
|
MAPK3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258991 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 11730323 |
Raf proteins have been shown to phosphorylate and activate MAPKKs (MAP kinase kinases) called MEKs (MAPK or ERK kinases) which in turn phosphorylate and activate MAPKs (MAP kinases) called ERKs |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
MEK1/2 | down-regulates activity
phosphorylation
|
CASP9 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270222 |
|
|
|
|
| pmid |
sentence |
| 12792650 |
Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2 |
|
| Publications: |
1 |
| Pathways: | COVID-19 Causal Network, Inhibition of Apoptosis |
| + |
BRAF | up-regulates
phosphorylation
|
MEK1/2 |
0.779 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244843 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8668348 |
We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide | down-regulates
chemical inhibition
|
MEK1/2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244854 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CHEK1 | down-regulates activity
|
MEK1/2 |
0.329 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263059 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28138032 |
Mechanistically, Ras-MEK signaling drives Chk1 expression and promotes cancer cell growth that produces genotoxic stress that requires Chk1 to mediate a response to the consequent DNA damage. Reciprocally, Chk1 engages a negative feedback loop to prevent hyperactivation of Ras-MEK signaling, thereby limiting DNA damage. Ras–MEK signaling transcriptionally activates Chk1, which appears to sustain cancer cell growth by maintaining DNA damage levels below a threshold that would otherwise drive apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
RAF1 | up-regulates activity
phosphorylation
|
MEK1/2 |
0.737 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244945 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11018021 |
The best characterized Raf substrates are MEK1 and MEK2. The activation of MEK1/2 by Raf is required to mediate many of the cellular responses to Raf activation, suggesting that MEK1/2 are the dominant Raf effector proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Ovary |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
MEK1/2 | up-regulates
binding
|
PPARG |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244971 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18596912 |
The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Rett syndrome, Thyroid cancer |
3.0
MEK1/2