Jak2 FERM domain interaction with the erythropoietin receptor regulates Jak2 kinase activity

Megumi Funakoshi-Tago, Stéphane Pelletier, Hiroshi Moritake, Evan Parganas, James N. Ihle

研究成果: Article査読

73 被引用数 (Scopus)

抄録

Janus kinases are essential for signal transduction by a variety of cytokine receptors and when inappropriately activated can cause hematopoietic disorders and oncogenesis. Consequently, it can be predicted that the interaction of the kinases with receptors and the events required for activation are highly controlled. In a screen to identify phosphorylation events regulating Jak2 activity in EpoR signaling, we identified a mutant (Jak2-Y613E) which has the property of being constitutively activated, as well as an inactivating mutation (Y766E). Although no evidence was obtained to indicate that either site is phosphorylated in signaling, the consequences of the Y613E mutation are similar to those observed with recently described activating mutations in Jak2 (Jak2-V617F and Jak2-L611S). However, unlike the V617F or L611S mutant, the Y613E mutant requires the presence of the receptor but not Epo stimulation for activation and downstream signaling. The properties of the Jak2-Y613E mutant suggest that under normal conditions, Jak2 that is not associated with a receptor is locked into an inactive state and receptor binding through the FERM domain relieves steric constraints, allowing the potential to be activated with receptor engagement.

本文言語English
ページ(範囲)1792-1801
ページ数10
ジャーナルMolecular and cellular biology
28
5
DOI
出版ステータスPublished - 2008 3月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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