Cdk4 Recombinant Rabbit Monoclonal Antibody [SD20-42]

Function

Cell cycle progression is controlled in part by a family of cyclin proteins and cyclin dependent kinases (Cdks). Cdk proteins work in concert with the cyclins to phosphorylate key substrates involved in each phase of cell cycle progression . Another family of proteins, Cdk inhibitors, also plays a role in regulating the cell cycle by binding to cyclin-Cdk complexes and modulating their activity. Several Cdk proteins have been identified, including Cdk2-Cdk8, PCTAIRE-1-PCTAIRE-3, PITALRE and PITSLRE. Cdk4, in complex with D-type cyclins, is thought to regulate cell growth during the G1 phase of the cell cycle. This association with a D-type cyclin upregulates Cdk4 activity, whereas binding to the Cdk inhibitor p16 downregulates Cdk4 activity. Activation of the Cdk4-cyclin complexes requires phosphorylation on a single threonyl residue of Cdk4, catalyzed by a Cdk-activating protein (CAK).

Background References

1. Machado-Neto, JA. et al. 2014. ANKHD1, a novel component of the Hippo signaling pathway, promotes YAP1 activation and cell cycle progression in prostate cancer cells. Exp. Cell Res.. 324: 137-45.

2. Liu, Y. et al. 2010. Rosiglitazone inhibits cell proliferation by inducing G1 cell cycle arrest and apoptosis in ADPKD cyst-lining epithelia cells. Basic Clin. Pharmacol. Toxicol.. 106: 523-530.

Sequence Similarity

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Post-translational Modification

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.

Subcellular Location

Nucleus, Nucleus membrane, Cytoplasm.

UNIPROT

SwissProt: P11802 Human

Synonyms