Retention of PDGFR-beta function in mice in the absence of phosphatidylinositol 3'-kinase and phospholipase Cgamma signaling pathways.
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.
Tallquist
M D
MD
Program in Developmental Biology and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Klinghoffer
R A
RA
Heuchel
R
R
Mueting-Nelsen
P F
PF
Corrin
P D
PD
Heldin
C H
CH
Johnson
R J
RJ
Soriano
P
P
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004789:Enzyme Activation; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005921:Glomerulonephritis / Q000473:pathology; D006720:Homozygote; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051966:Phospholipase C gamma; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D010738:Type C Phospholipases; D051966:Phospholipase C gamma