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 study, 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 substrate to assess the sites of Bmx expression revealed strong signals in the endothelial cells of large arteries and in the endocardium starting between 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 inferior venae cavae. Of the five known endothelial receptor tyrosine kinases tested, activated Tie-2 induced tyrosyl phosphorylation of the Bmx protein and both Tie-2 and vascular endothelial growth factor receptor 1 (VEGFR-1) stimulated Bmx tyrosine kinase activity. Thus, the Bmx tyrosine kinase has a redundant role in arterial endothelial signal transduction downstream of the Tie-2 and VEGFR-1 growth factor receptors.
Rajantie
I
I
Molecular/Cancer Biology Laboratory, Haartman Institute and Biomedicum Helsinki, 00014 University of Helsinki, Finland.
Ekman
N
N
Iljin
K
K
Arighi
E
E
Gunji
Y
Y
Kaukonen
J
J
Palotie
A
A
Dewerchin
M
M
Carmeliet
P
P
Alitalo
K
K
D042683:Angiopoietin-1; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007763:Lac Operon; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042787:Receptor, TIE-2; D015398:Signal Transduction / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; C105373:MEN1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C492367:BMX protein, human; C492366:Bmx protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1