cyclin-dependent kinase-4 (CDK4) or PSK-J3

Function

• major catalytic subunit of mammalian D-type cyclins
• role in control of the cell cycle (putative)
• constitutively expressed throughout the cell cycle
• forms a stable complex with D-type G1 cyclins
• assembly & accumulation of functional CDK4/cyclin-D complexes that is rate limiting for progression through G1
• once formed, the CDK4/cyclin-D complex must be activated by phosphorylation of Thr-172 on CDK4, a reaction catalyzed by CAK
• complex formation & phosphorylation are independently regulated events
• phosphorylation of CDK4 subunit of CDK4/cyclin-D complex is subject to regulation by both stimulatory & inhibitory cytokine signals thus allowing CDK4 to function in a mid G1 checkpoint
• CDK4 is also regulated by the binding of p15INK4/MTS1 while in complex with cyclin D independent of phosphorylation status
• interacts with SEI1 & ZNF655/VIK
• phosphorylation at Thr-172 is necessary for enzymatic activity (putative)

Structure

• belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family
• CDC2/CDKX subfamily contains 1 protein kinase domain

Pathology

• CDK4 mutations are involved in tumor formation defects in CDK4 are the cause of cutaneous malignant melanoma 3

More general terms

• cyclin-dependent kinase (CDK)

Component of

• CDK4/cyclin D complex
• CDK4/cyclin D1 complex

Database

• UniProt: http://www.uniprot.org/uniprot/P11802.html
• OMIM: https://mirror.omim.org/entry/123829
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1019