The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions.
Gene targeting studies have indicated that the two receptors for PDGF, alpha and beta, direct unique functions during development. Distinct ligand affinities, patterns of gene expression, and/or mechanisms of signal relay may account for functional specificity of the two PDGF receptor isoforms. To distinguish between these factors, we have created two complementary lines of knockin mice in which the intracellular signaling domains of one PDGFR have been removed and replaced by those of the other PDGFR. While both lines demonstrated substantial rescue of normal development, substitution of the PDGFbetaR signaling domains with those of the PDGFalphaR resulted in varying degrees of vascular disease. This observation provides a framework for discussing the evolution of receptor tyrosine kinase functional specificity.
Program in Developmental Biology and Division, Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
R A
RA
Klinghoffer
P F
PF
Mueting-Nelsen
A
A
Faerman
M
M
Shani
P
P
Soriano
D000818:Animals; D002478:Cells, Cultured; D017353:Gene Deletion; D018390:Gene Targeting / Q000379:methods; D005816:Genetic Complementation Test; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology; D006651:Histocytochemistry; D007668:Kidney / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D015398:Signal Transduction; D013927:Thrombosis / Q000235:genetics / Q000473:pathology; D013997:Time Factors
D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D020928:Mitogen-Activated Protein Kinases