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Jak2 tyrosine kinase interacts with and tyrosine phosphorylates tubulin
Author(s) -
Ma Xianyue,
Sayeski Peter P
Publication year - 2006
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.20.5.a1200-b
Subject(s) - tyrosine phosphorylation , sh2 domain , phosphorylation , tyrosine , receptor tyrosine kinase , protein tyrosine phosphatase , proto oncogene tyrosine protein kinase src , tubulin , tyrosine kinase , biology , microbiology and biotechnology , protein phosphorylation , signal transduction , microtubule , chemistry , biochemistry , protein kinase a
Jak2 is a non‐receptor tyrosine kinase and acts as a key intermediate in linking ligand binding at the cell surface with the modulation of gene transcription in the nucleus. Here, we report that new substrates of Jak2 were identified. Large amounts of recombinant Jak2 protein were made in cultured cells using a vaccinia virus‐mediated expression system. Immunoaffinity purification was used to isolate Jak2 protein. An unknown protein of 55 kDa in mass specifically co‐purified with Jak2. Interestingly, the 55 kDa protein could be phosphorylated on tyrosine residues and this phosphorylation was correspondent to the tyrosine phosphorylation levels of Jak2. Mass spectrometry and Western blot analysis identified the 55 kDa protein as the [alpha]‐ and [beta]‐ isoforms of tubulin. Biochemical experiments determined that Jak2 and tubulin specifically co‐associate with one another and the region of Jak2 that binds tubulin is the pseudokinase domain. Indirect immunofluoresence indicated that Jak2 co‐localized with the microtubules of the cell. The functional consequence of this interaction of Jak2 and tubulin is that Jak2 phosphorylates tubulin on tyrosine residues. As such, this work demonstrates that Jak2 is a tubulin kinase and Jak2 may modulate signal transduction via the tyrosine phosphorylation of [alpha]‐ and [beta]‐ tubulin. Support: AHA (#0555359B, 0425378B), NIH (K01‐DK60471, R01‐HL67277)