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Molecular and Cellular Biology, July 2001, p. 4647-4655, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4647-4655.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Bmx Tyrosine Kinase Has a Redundant Function Downstream of Angiopoietin and Vascular Endothelial Growth Factor Receptors in Arterial Endothelium

Iiro Rajantie,1 Niklas Ekman,1 Kristiina Iljin,1 Elena Arighi,1 Yuji Gunji,1 Jaakko Kaukonen,2 Aarno Palotie,2 Mieke Dewerchin,3 Peter Carmeliet,3 and Kari Alitalo1,*

Molecular/Cancer Biology Laboratory, Haartman Institute and Biomedicum Helsinki,1 and Department of Clinical Chemistry and Helsinki University Hospital,2 00014 University of Helsinki, Finland, and Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Campus Gasthuisberg, University of Leuven, Leuven B-3000, Belgium3

Received 14 February 2001/Returned for modification 23 March 2001/Accepted 25 April 2001

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.

* Corresponding author. Mailing address: Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), 00014 University of Helsinki, Finland. Phone: 358-9-1912 5511. Fax: 358-9-1912 5510. E-mail: Kari.Alitalo{at}Helsinki.FI.

Molecular and Cellular Biology, July 2001, p. 4647-4655, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4647-4655.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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