Reactome | PTK6 phosphorylates CDKN1B

PTK6 phosphorylates CDKN1B

Stable Identifier

R-HSA-8848436

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

BRK phosphorylates p27KIP1

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Cell Cycle, Mitotic (Homo sapiens)
  - Mitotic G1 phase and G1/S transition (Homo sapiens)
    - G1/S Transition (Homo sapiens)
      - Cyclin E associated events during G1/S transition (Homo sapiens)
        
        SCF(Skp2)-mediated degradation of p27/p21 (Homo sapiens)
        
        PTK6 phosphorylates CDKN1B (Homo sapiens)
  - S Phase (Homo sapiens)
    - Cyclin A:Cdk2-associated events at S phase entry (Homo sapiens)
      - SCF(Skp2)-mediated degradation of p27/p21 (Homo sapiens)
        
        PTK6 phosphorylates CDKN1B (Homo sapiens)

General

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PTK6 (BRK) phosphorylates CDKN1B (p27KIP1) bound to the complex of CDK4 and CCND1 (cyclin D1) on tyrosine residue Y88 and possibly other tyrosines (e.g. Y89) (Patel et al. 2015). Based on the finding that PTK6 promotes ERBB2-induced increase in cyclin E1 (CCNE1) levels and decrease in CDKN1B levels (Xiang et al. 2008), and supported by the analogy with other SRC family kinases that phosphorylate CDKN1B (Grimmler et al. 2007), PTK6 is likely to also phosphorylate CDKN1B bound to the complex of CCNE1 and CDK2. Phosphorylation of CDKN1B (p27KIP1) on tyrosine residue Y88 by SRC family kinases dislodges the 3-10 helix of CDKN1B from the active site of CDK2 or CDK4, thus converting CDKN1B from a bound inhibitor to a bound non-inhibitor (Grimmler et al. 2007, Ray et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
25733683	Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4 Wagner, R, Patel, P, Asbach, B, Blain, SW, Coltoff, A, Shteyn, E, Gomez, C, Bhuyan, S, Tyner, AL	Mol. Cell. Biol.	2015