Relation Results

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276888	Ser110	GEDSLEQsPLLEDKY	Mus musculus	NIH-3T3 Cell
pmid	sentence
25733682	MEF2C and MEF2D interact with the E3 ligase F-box protein SKP2, which mediates their subsequent degradation through the ubiquitin-proteasome system. The cyclin-dependent kinase 4 (CDK4)/cyclin D1 complex phosphorylates MEF2D on serine residues 98 and 110, and phosphorylation of these residues is an important determinant for SKP2 binding.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276887	Ser98	KGFNGCDsPEPDGED	Mus musculus	NIH-3T3 Cell
pmid	sentence
25733682	MEF2C and MEF2D interact with the E3 ligase F-box protein SKP2, which mediates their subsequent degradation through the ubiquitin-proteasome system. The cyclin-dependent kinase 4 (CDK4)/cyclin D1 complex phosphorylates MEF2D on serine residues 98 and 110, and phosphorylation of these residues is an important determinant for SKP2 binding.

Publications:

2

Organism:

Mus Musculus

Pathways:

IGF and Myogenesis

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276087	Ser12	KTLYSFFsPSPARKR	Homo sapiens	HeLa Cell
pmid	sentence
18079698	We investigated the ability of four active CDK/cyclin pairs to phosphorylate UNG2 in vitro.When UNG2 was subjected to in vitro phosphorylation by either of these sets of CDK/cyclins, multiple phosphorylated forms of UNG2 were observed (Figure 5B). Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases.Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases (Figure 5B, upper panels) in agreement with the accumulation of this phosphorylation in G2 (Figure 3B). In addition, (unspecific) phosphorylation by all kinases was observed at S12 and S14.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276085	Ser14	LYSFFSPsPARKRHA	Homo sapiens	HeLa Cell
pmid	sentence
18079698	We investigated the ability of four active CDK/cyclin pairs to phosphorylate UNG2 in vitro.When UNG2 was subjected to in vitro phosphorylation by either of these sets of CDK/cyclins, multiple phosphorylated forms of UNG2 were observed (Figure 5B). Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases.Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases (Figure 5B, upper panels) in agreement with the accumulation of this phosphorylation in G2 (Figure 3B). In addition, (unspecific) phosphorylation by all kinases was observed at S12 and S14.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276084	Ser23	ARKRHAPsPEPAVQG	Homo sapiens	HeLa Cell
pmid	sentence
18079698	We investigated the ability of four active CDK/cyclin pairs to phosphorylate UNG2 in vitro.When UNG2 was subjected to in vitro phosphorylation by either of these sets of CDK/cyclins, multiple phosphorylated forms of UNG2 were observed (Figure 5B). Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases.Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases (Figure 5B, upper panels) in agreement with the accumulation of this phosphorylation in G2 (Figure 3B). In addition, (unspecific) phosphorylation by all kinases was observed at S12 and S14.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276086	Thr60	AGQEEPGtPPSSPLS	Homo sapiens	HeLa Cell
pmid	sentence
18079698	We investigated the ability of four active CDK/cyclin pairs to phosphorylate UNG2 in vitro.When UNG2 was subjected to in vitro phosphorylation by either of these sets of CDK/cyclins, multiple phosphorylated forms of UNG2 were observed (Figure 5B). Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases.Mass spectrometry analyses revealed that the ‘early' CDK4/cyclin D and CDK2/cyclin E kinases were able to phosphorylate all three UNG2 Ser/Thr residues observed in vivo (only CDK2/cyclin E shown). Of these, only S64 was phosphorylated by the ‘late' CDK2/cyclin A and CDK1/cyclin B kinases (Figure 5B, upper panels) in agreement with the accumulation of this phosphorylation in G2 (Figure 3B). In addition, (unspecific) phosphorylation by all kinases was observed at S12 and S14.

Publications:

4

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-274099	Ser1217	MSLENPLsPFSSDIN	Homo sapiens	HEK-293 Cell
pmid	sentence
32294430	We show here that CyclinD-Cdk4/6 activates mTORC1 by binding and phosphorylating TSC2 on Ser1217 and Ser1452.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-274100	Ser1452	LPSSSPRsPSGLRPR	Homo sapiens	HEK-293 Cell
pmid	sentence
32294430	We show here that CyclinD-Cdk4/6 activates mTORC1 by binding and phosphorylating TSC2 on Ser1217 and Ser1452.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-216976	Ser207	TSVRRRTsFYLPKDA	Homo sapiens
pmid	sentence
18071316	This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-216980	Ser356	SSSGGDRsPTRMLAS	Homo sapiens
pmid	sentence
19351720	Our findings demonstrate that the cell cycle proteins cyclin d1 and cdk4 induce runx2 and runx3 phosphorylation, ubiquitylation and proteasomal degradation.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence
SIGNOR-275496	Ser372	EEIYGANsPIWESGF
pmid	sentence
24870244	Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5\|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)

Identifier	Residue	Sequence
SIGNOR-275497	Thr272	LNYWKLEtPAQFRQR
pmid	sentence
24870244	Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5\|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)

Publications:

2

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-277340	Ser40	ASAAGGLsPVTNLTV	Homo sapiens	A-431 Cell
pmid	sentence
28192398	We demonstrate that CyclinD-CDK4/CDK6 complexes mediate the phosphorylation of CDC25A on Ser40 during G1 and that these complexes directly phosphorylate this residue in vitro. Importantly, we also find that CyclinD1-CDK4 decreases CDC25A stability in a ßTrCP-dependent manner and that Ser40 and Ser88 phosphorylations contribute to this regulation.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-277342	Ser88	DSGFCLDsPGPLDSK	Homo sapiens	A-431 Cell
pmid	sentence
28192398	We demonstrate that CyclinD-CDK4/CDK6 complexes mediate the phosphorylation of CDC25A on Ser40 during G1 and that these complexes directly phosphorylate this residue in vitro. Importantly, we also find that CyclinD1-CDK4 decreases CDC25A stability in a ßTrCP-dependent manner and that Ser40 and Ser88 phosphorylations contribute to this regulation.

Publications:

2

Organism:

Homo Sapiens

Pathways:

Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-250754	Ser484	ERGKLPEsPKRAEEI	Mus musculus	NIH-3T3 Cell
pmid	sentence
10202152	We have identified Ser484 as a direct target for cyclin-dependent kinase 4 (cdk4)-cyclin D1- and cdk2-cyclin E-directed phosphorylation. Mutation of Ser484 impairs rDNA transcription in vivo and in vitro.

Publications:

1

Organism:

Mus Musculus

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-216984	Ser632	LVVSRNLsPPNCTEL	Homo sapiens	Breast Cancer Cell
pmid	sentence
17334399	In particular, we have identified ser 632 of brca1 as a cyclin d1/cdk4 phosphorylation site in vitro. Using chromatin immunoprecipitation assays, we observed that the inhibition of cyclin d1/cdk4 activity resulted in increased brca1 dna binding at particular promoters in vivo.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Cell cycle: G2/M phase transition

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-216988	Ser780	STRPPTLsPIPHIPR	Homo sapiens	Breast Cancer Cell
pmid	sentence
23336272	Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression.

Identifier	Residue	Sequence	Organism
SIGNOR-250759	Ser788	PIPHIPRsPYKFPSS	in vitro
pmid	sentence
9139732	In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-216992	Ser795	SPYKFPSsPLRIPGG	Homo sapiens	Breast Cancer Cell
pmid	sentence
23336272	Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression.

Identifier	Residue	Sequence	Organism
SIGNOR-250760	Thr356	DSFETQRtPRKSNLD	in vitro
pmid	sentence
9139732	In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB.

Identifier	Residue	Sequence	Organism
SIGNOR-250762	Thr5	tPRKTAAT	in vitro
pmid	sentence
9139732	In summary, we have shown evidence that CDK4-cyclin D1 phosphorylates Thr5, Ser249, Thr252, Thr356, Thr373, Ser788, Ser795, Ser807, Ser811, and Thr826 of pRB.

Identifier	Residue	Sequence	Organism
SIGNOR-216957	Thr826	LPTPTKMtPRSRILV	Homo sapiens
pmid	sentence
9139732	We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein.

Publications:

6

Organism:

Homo Sapiens, In Vitro

Pathways:

Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, IGF and Myogenesis, Pancreatic ductal adenocarcinoma (PDA), Rhabdomyosarcoma

Identifier	Residue	Organism
SIGNOR-217514		Homo sapiens
pmid	sentence
8891723	The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks,cdk4and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb.

Identifier	Residue	Organism
SIGNOR-245459		Homo sapiens
pmid	sentence
11154267	Overexpression of p16INK4a in cells with functional pRb results in inhibition of both Cdk4- and Cdk6-associated kinase activity and pRb phosphorylation, with subsequent cell cycle arrest (46, 50). In addition, inhibition of D cyclin-Cdk4 complex formation by p16INK4a prevents sequestration of p21Cip1 and p27Kip1 by these complexes in early G1, leading to suppression of cyclin E-Cdk2 activity

Publications:

2

Organism:

Homo Sapiens

Pathways:

Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Pancreatic ductal adenocarcinoma (PDA), Rhabdomyosarcoma

Identifier	Residue	Organism
SIGNOR-32301		Homo sapiens
pmid	sentence
7736585	D-type cyclins (cyclin d1, d2, or d3) and their associated cyclin-dependent kinases (cdk4, cdk6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the g1 restriction point and into the s phase when activated by cyclin d1, cdk4 is able to phosphorylate prb,

Publications:

1

Organism:

Homo Sapiens

Pathways:

Pancreatic ductal adenocarcinoma (PDA)

Identifier	Residue	Organism
SIGNOR-245432		Homo sapiens
pmid	sentence
23552696	Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1

Publications:

1

Organism:

Homo Sapiens

Pathways:

Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, IGF and Myogenesis

Identifier	Residue	Organism
SIGNOR-216972		Homo sapiens
pmid	sentence
21902831	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

Publications:

1

Organism:

Homo Sapiens

Pathways:

IGF and Myogenesis, Rhabdomyosarcoma

Identifier	Residue	Organism
SIGNOR-216963		Homo sapiens
pmid	sentence
21902831	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

Publications:

1

Organism:

Homo Sapiens

Pathways:

IGF and Myogenesis

Identifier	Residue	Organism	Cell Line
SIGNOR-245456		Homo sapiens	HEK-293 Cell
pmid	sentence
23429262	We show that the miRNA-induced silencing of CDC25A increases the tyrosine phosphorylation status of CDK4/6 cyclin-dependent kinases which, in turn, abolishes CDK4/6 capacity to associate with D-type cyclins. This prevents CDK4/6 kinases activation, impairs downstream events such as cyclin E stimulation and sequesters cells in early G1.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-272089
pmid	sentence
18583321	We performed immunoprecipitation and western blotting analysis in transfected cell lines using CDK4 and cyclin D1 antibodies. As expected, cells transfected with AQP5 WT showed an increase of the CDK4/cyclin D1 complex, whereas cells transfected with vector did not\|hAQP5 Increases Phosphorylation of Retinoblastoma Protein through Cyclin D1/CDK4 Complex

Publications:

1

Identifier	Residue	Organism
SIGNOR-216960		Homo sapiens
pmid	sentence
21902831	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

Publications:

1

Organism:

Homo Sapiens

Pathways:

IGF and Myogenesis

Identifier	Residue	Organism
SIGNOR-32298		Homo sapiens
pmid	sentence
7736585	D-type cyclins (cyclin d1, d2, or d3) and their associated cyclin-dependent kinases (cdk4, cdk6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the g1 restriction point and into the s phase when activated by cyclin d1, cdk4 is able to phosphorylate prb,

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-216966		Homo sapiens
pmid	sentence
21902831	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

Publications:

1

Organism:

Homo Sapiens

Pathways:

IGF and Myogenesis

Identifier	Residue	Organism
SIGNOR-216969		Homo sapiens
pmid	sentence
21902831	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

Publications:

1

Organism:

Homo Sapiens

Pathways:

IGF and Myogenesis, Rhabdomyosarcoma

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273193
pmid	sentence
12640120	Transition through this point requires cdk6/4-cyclin D, since inhibition with TAT-p16INK4A during the first 3 to 5 h prevents cell cycle entry and maintains both naive and memory T cells in G0.

Publications:

1

Name	CyclinD/CDK4 View Modifications
Primary ID	SIGNOR-C18
Links	CPX-2010
Type	complex
Formed by	CCND1, CDK4
Relations	35
Pathways	Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Pancreatic ductal adenocarcinoma (PDA), Rhabdomyosarcoma

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