The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions

Gene targeting studies have indicated that the two receptors for PDGF, alph a and beta, direct unique functions during development. Distinct ligand aff inities, patterns of gene expression, and/or mechanisms of signal relay may account for functional specificity of the two PDGF receptor isoforms. To d istinguish between these factors, we have created two complementary lines o f knockin mice in which the intracellular signaling domains of one PDGFR ha ve been removed and replaced by those of the other PDGFR. While both lines demonstrated substantial rescue of normal development, substitution of the PDGF betaR signaling domains with those of the PDGF alphaR resulted in vary ing degrees of vascular disease. This observation provides a framework for discussing the evolution of receptor tyrosine kinase functional specificity .