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CDK4  Protein, Antibody, ELISA Kit, cDNA Clone

Expression host: Baculovirus-Insect Cells  
10732-H09B-50
50 µg 
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CDK4 Related Area

CDK4 Related Pathways

CDK4 Related Protein, Antibody, cDNA Gene, and ELISA Kits

CDK4 Related Protein, Antibody, cDNA Gene, and ELISA Kits

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CDK4 Summary & Protein Information

CDK4 Background

Catalytic activity: ATP + a protein = ADP + a phosphoprotein. {ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:9106657}.
Enzyme regulation: ENZYME REGULATION: Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequennt activation. {ECO:0000269|PubMed:19487459}.
Subunit structure: Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with SEI1 and ZNF655. Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex. The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression. Interacts with CEBPA (when phosphorylated) (PubMed:15107404). {ECO:0000250|UniProtKB:P30285, ECO:0000269|PubMed:10580009, ECO:0000269|PubMed:15107404, ECO:0000269|PubMed:15558030, ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:19124461, ECO:0000269|PubMed:19237555, ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:9106657}.
Subcellular location: Cytoplasm. Nucleus. Membrane. Note=Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1) phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1) to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.
Post-translational: Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B. {ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:19237555, ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:19487459}.
Involvement in disease: DISEASE: Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites. {ECO:0000269|PubMed:7652577, ECO:0000269|PubMed:8528263, ECO:0000269|PubMed:9311594, ECO:0000269|PubMed:9425228}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Sequence similarity: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.; Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
General information above from UniProt

CDK4 is a member of the Ser/Thr protein kinase family. It is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of CDK4 is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). CDK4 was shown to be responsible for the phosphorylation of retinoblastoma gene product. CDK4 is the ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. CDK4 has been shown to be mutated in some types of cancer, whilst a chromosomal rearrangement can lead to Cdk6 overexpression in lymphoma, leukemia and melanoma.

CDK4 Alternative Name

CMM3,PSK-J3, [homo-sapiens]
CDK4,CMM3,MGC14458,PSK-J3, [human]
Cdk4,Crk3, [mouse]
Crk3, [mus-musculus]

CDK4 Related Studies

  • Stepanova L, et al. (1996) Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 10(12):1491-502.
  • Lamphere L, et al. (1997) Interaction between Cdc37 and Cdk4 in human cells. Oncogene. 14(16): 1999-2004.
  • Dai K, et al. (1996) Physical interaction of mammalian CDC37 with CDK4. J Biol Chem. 271(36): 22030-4.
  • Sugimoto M, et al. (1999) Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1. Genes Dev. 13(22):3027-33.
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