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Tyrosine 972 is Critical for Jak2 Tyrosine Kinase Function
Author(s) -
McDoom Issam,
Sayyah Jacqueline,
Sayeski Peter P.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1211-c
Subject(s) - autophosphorylation , janus kinase 2 , phosphorylation , tyrosine kinase , receptor tyrosine kinase , mutation , microbiology and biotechnology , tyrosine , tyrosine phosphorylation , jak stat signaling pathway , janus kinase , signal transduction , ror1 , function (biology) , kinase , cancer research , chemistry , biology , receptor , biochemistry , platelet derived growth factor receptor , protein kinase a , gene , growth factor
Janus Kinase 2 (Jak2) is a non‐receptor tyrosine kinase that links ligand/receptor interactions at the cell surface to transcriptional alterations in the nucleus. Phosphotyrosine residues play an important role in regulationg Jak2 function. Here, we sought to determine the role of a novel phosphotyrosine, Y972, on Jak2 function. We hypothesized that phosphorylation of Jak2 at position 972 is critical for achieving full Jak2 function. To test this, we produced a mutant Jak2 expressing a tyrosine to phenylalanine point mutation at position 972 (Y972F) and investigated the effects of this mutation on several aspects of Jak2 function. Specifically, we determined that the Y972F mutation significantly reduced Jak2 autophosphorylation. We showed that this loss results from a decrease in Jak2 kinase function. The Y972F loss of function impaired the ability of Jak2 to phosphorylate SH2B‐β, but did not hinder the ability of Jak2 to bind SH2B‐β. We also found that the Y972F mutation significantly affected the ability of Jak2 to become activated by SH2B‐β. The Y972F mutation hindered growth hormone dependent Jak2 activation and STAT1 nuclear translocation. In conclusion, phosphorylation at Y972 is critical for maximal Jak2 function and in turn affects Jak2‐dependent signaling.