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Genes & Dev. 14 (24): 3179-3190

Copyright © 2000 by Cold Spring Harbor Laboratory Press.

Vol. 14, No. 24, pp. 3179-3190, December 15, 2000

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

Michelle D. Tallquist,1 Richard A. Klinghoffer,1 Rainer Heuchel,2 Peter F. Mueting-Nelsen,1 Philip D. Corrin,1 Carl-Henrik Heldin,2 Richard J. Johnson,3 and Philippe Soriano1,4

1 Program in Developmental Biology and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; 2 Ludwig Institute for Cancer Research, Biomedical Center, S-751 24 Uppsala, Sweden; 3 Division of Nephrology, University of Washington, Seattle, Washington 98109, USA

Signal transduction by the platelet-derived growth-factor receptor beta  (PDGFR-beta ) tyrosine kinase is required for proper formation of vascular smooth muscle cells (VSMC). However, the importance of individual PDGFR-beta 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-beta that can no longer activate PI3kinase or PLCgamma . 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-beta operates at suboptimal levels. Our observations indicate that although loss of these pathways can lead to attenuated PDGF-dependent cellular function, certain PDGFR-beta -induced signal cascades are not essential for survival in mice.

[Key Words: PDGF; PI3kinase; phospholipase C; chimera; mesangial cells]

4 Corresponding author.

GENES & DEVELOPMENT 14:3179-3190 © 2000 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/00 $5.00

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