Bcr in Vascular Smooth Muscle Cells

Involvement of Ras and Raf-1 Activation by Bcr


Address for correspondence: Jun-ichi Abe, M.D., Ph.D., Center for Cardiovascular Research, Box 679, 601 Elmwood Avenue, Rochester, NY 14642. Voice: 716-273-1686; fax: 716-275-9895; jun-ichi_abe@urmc.rochester.edu.


Abstract: Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene. In vascular smooth muscle cells, platelet-derived growth factor-BB (PDGF) stimulated Bcr kinase activity. The mutant PDGF receptor for PI3-K, but not for PLC-γ binding sites, showed significantly reduced Bcr kinase activity. Bcr wild-type enhanced, whereas Bcr kinase negative form inhibited PDGF-stimulated ERK1/2 activity. A dominant negative Ras did not inhibit Bcr kinase activation, and overexpression of Bcr increased Ras/Raf-1 activity and DNA synthesis. These results demonstrated the importance of Bcr in PDGF-mediated events such as activation of Ras, Raf-1, and ERK1/2 and stimulation of DNA synthesis.