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Bruton's tyrosine kinase (BTK) is a binding partner for hypoxia induced mitogenic factor (HIMF/FIZZ1) and mediates myeloid cell chemotaxis.

Authors
  • Su, Qingning
  • Zhou, Yifu
  • Johns, Roger A
Type
Published Article
Journal
The FASEB Journal
Publisher
Federation of American Society for Experimental Biology
Publication Date
May 01, 2007
Volume
21
Issue
7
Pages
1376–1382
Identifiers
PMID: 17264170
Source
Medline
License
Unknown

Abstract

Hypoxia induced mitogenic factor (HIMF) is a member of the FIZZ/resistin/RELM family of proteins that we have shown to have potent mitogenic, angiogenic, and vasoconstrictive effects in the lung vasculature. In the current report, we identified Bruton's tyrosine kinase (BTK) as a functional HIMF binding partner through glutathione S-transferase (GST)-HIMF pull-down studies and mass spectrometry. Using primary cultured HIMF-stimulated murine bone marrow cells, we demonstrated that HIMF causes redistribution of BTK to the leading edge of the cells. HIMF stimulation induced BTK autophosphorylation, which peaked at 2.5 min. A transwell migration assay showed that treatment with recombinant murine HIMF induced migration of primary cultured bone marrow cells that was completely blocked by the BTK inhibitor, LFM-A13. Our results demonstrate BTK as the first known functional binding partner of the HIMF/FIZZ family of proteins and that HIMF acts as a chemotatic molecule in stimulating the migration of myeloid cells through activation of the BTK pathway.

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