Retention of PDGFR-β function in mice in the absence of phosphatidylinositol 3′-kinase anti phospholipase Cγ signaling pathways

Abstract

Signal transduction by the platelet-derived growth-factor receptor β (PDGFR-β) tyrosine kinase is required for proper formation of vascular smooth muscle cells (VSMC). However, the importance of individual PDGFR-β signal transduction pathways in vivo is not known. To investigate the role of two of the pathways believed to be critical for PDGF signal transduction, we have generated mice that bear a PDGFR-β that can no longer activate PI3kinase or PLCγ. Although these mutant mice have normal vasculature, we provide multiple lines of evidence in vivo and from cells derived from the mutant mice that suggest that the mutant PDGFR-β operates at suboptimal levels. Our observations indicate that although loss of these pathways can lead to attenuated PDGF-dependent cellular function, certain PDGFR-β-induced signal cascades are not essential for survival in mice.