Abstract:
:The leptin receptor, LRb, and other cytokine receptors are devoid of intrinsic enzymatic activity and rely upon the activity of constitutively associated Jak family tyrosine kinases to mediate intracellular signaling. In order to clarify mechanisms by which Jak2, the cognate LRb-associated Jak kinase, is regulated and mediates downstream signaling, we employed tandem mass spectroscopic analysis to identify phosphorylation sites on Jak2. We identified Ser523 as the first-described site of Jak2 serine phosphorylation and demonstrated that this site is phosphorylated on Jak2 from intact cells and mouse spleen. Ser523 was highly phosphorylated in HEK293 cells independently of LRb-Jak2 activation, suggesting a potential role for the phosphorylation of Ser523 in the regulation of LRb by other pathways. Indeed, mutation of Ser523 sensitized and prolonged signaling by Jak2 following activation by the intracellular domain of LRb. The effect of Ser523 on Jak2 function was independent of Tyr570-mediated inhibition. Thus, the phosphorylation of Jak2 on Ser523 inhibits Jak2 activity and represents a novel mechanism for the regulation of Jak2-dependent cytokine signaling.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Ishida-Takahashi R,Rosario F,Gong Y,Kopp K,Stancheva Z,Chen X,Feener EP,Myers MG Jrdoi
10.1128/MCB.01589-05subject
Has Abstractpub_date
2006-06-01 00:00:00pages
4063-73issue
11eissn
0270-7306issn
1098-5549pii
26/11/4063journal_volume
26pub_type
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