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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

Interactions

molecular events

Related

cdk4 gene

General

cyclin-dependent kinase (CDK)

Properties

SIZE: MW = 34 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: Thr phosphorylation site {N-TERMINAL} Tyr phosphorylation site {N-TERMINAL} kinase domain MOTIF: ATP-binding site NAME: ATP-binding site PSTAIRE motif MOTIF-SEQUENCE: PSTAIRE Thr-phosphate binding site FOR-BINDING-OF: cyclin Thr-phosphate {T172}

References

  1. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS 3rd, Johnson BE, Skolnick MH. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994 Apr 15;264(5157):436-40. PMID: 8153634
  2. Marx [Research News] Science 264:344 1994
  3. Solomon MJ. The function(s) of CAK, the p34cdc2-activating kinase. Trends Biochem Sci. 1994 Nov;19(11):496-500. PMID: 7855894
  4. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CDK4
  5. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/CDK4ID238ch12q14.html
  6. UniProt :accession P11802

Component-of

CDK4/cyclin D complex

Databases & Figures

OMIM 123829 MORBIDMAP 123829 UniProt P11802 Entrez Gene 1019 Figures/diagrams/slides/tables related to cyclin-dependent kinase-4 (CDK4)