Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control.

ABSTRACT: Janus kinase 2 (JAK2) couples ligand activation of cell surface cytokine receptors to the regulation of cellular functions including cell cycle progression, differentiation and apoptosis. It thereby coordinates biological programs such as development and hematopoiesis. Unscheduled activation of JAK2 by point mutations or chromosomal translocations can induce hyperproliferation and hematological malignancies. Typical signal transduction by the JAK2 tyrosine kinase comprises phosphorylation of STAT transcription factors. In this study, we describe the identification of the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) as a novel JAK2 substrate. JAK2 can directly bind and phosphorylate p27(Kip1). Both, the JAK2 FERM domain and its kinase domain bind to p27(Kip1). JAK2 phosphorylates tyros

SUBMITTER: Jakel H 

PROVIDER: S-EPMC3160490 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature