Retention of PDGFR-beta function in mice in the absence of phosphatidylinositol 3 '-kinase and phospholipase C gamma signaling pathways

Signal transduction by the platelet-derived growth-factor receptor beta (PD GFR-beta) tyrosine kinase is required for proper formation of vascular smoo th muscle cells (VSMC). However, the importance of individual PDGFR-beta si gnal 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-beta that can no longer activate P I3kinase or PLC gamma. Although these mutant mice have normal vasculature, we provide multiple lines of evidence in vivo and from cells derived from t he mutant mice that suggest that the mutant PDGFR-beta operates at suboptim al levels. Our observations indicate that although loss of these pathways c an lead to attenuated PDGF-dependent cellular function, certain PDGFR-beta -induced signal cascades are not essential for survival in mice.