Bruton's tyrosine kinase (BTK) is a binding partner for hypoxia induced mitogenic factor (HIMF/FIZZ1) and mediates myeloid cell chemotaxis.
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.
Su
Qingning
Q
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205, USA.
Zhou
Yifu
Y
Johns
Roger A
RA
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D002460:Cell Line; D002633:Chemotaxis; D017931:DNA Primers; D005982:Glutathione Transferase / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C413576:Retnla protein, mouse; D020932:Nerve Growth Factor; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse