Bmx tyrosine kinase has a redundant function downstream of angiopoietin and vascular endothelial growth factor receptors in arterial endothelium

The Bmx gene, a member of the Tec tyrosine kinase gene family, is known to be expressed in subsets of hematopoietic and endothelial cells. In this stu dy, mice were generated in which the first coding exon of the Bmx gene was replaced with the lacZ reporter gene by a knock-in strategy. The homozygous mice lacking Bmx activity were fertile and had a normal life span without an obvious phenotype. Staining of their tissues using beta -galactosidase s ubstrate to assess the sites of Bmx expression revealed strong signals in t he endothelial cells of large arteries and in the endocardium starting betw een days 10.5 and 12.5 of embryogenesis and continuing in adult mice, while the venular endothelium showed a weak signal only in the superior and infe rior venae cavae. Of the five known endothelial receptor tyrosine kinases t ested, activated Tie-2 induced tyrosyl phosphorylation of the Bmx protein a nd both Tie-2 and vascular endothelial growth factor receptor 1 (VEGFR-1) s timulated Bmx tyrosine kinase activity. Thus, the Bmx tyrosine kinase has a redundant role in arterial endothelial signal transduction downstream of t he Tie-2 and VEGFR-1 growth factor receptors.