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Molecular Cell
Klinghoffer, R.A., Program in Developmental Biology and Division, Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
Mueting-Nelsen, P.F., Program in Developmental Biology and Division, Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
Faerman, A., Institute of Animal Science, The Volcani Center, Bet Dagan 50250, Israel
Shani, M., Institute of Animal Science, The Volcani Center, Bet Dagan 50250, Israel
Soriano, P., Program in Developmental Biology and Division, Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
Gene targeting studies have indicated that the two receptors for PDGF, α and β, 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 PDGFβR signaling domains with those of the PDGFαR resulted in varying degrees of vascular disease. This observation provides a framework for discussing the evolution of receptor tyrosine kinase functional specificity.
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The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions
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Klinghoffer, R.A., Program in Developmental Biology and Division, Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
Mueting-Nelsen, P.F., Program in Developmental Biology and Division, Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
Faerman, A., Institute of Animal Science, The Volcani Center, Bet Dagan 50250, Israel
Shani, M., Institute of Animal Science, The Volcani Center, Bet Dagan 50250, Israel
Soriano, P., Program in Developmental Biology and Division, Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States
The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions
Gene targeting studies have indicated that the two receptors for PDGF, α and β, 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 PDGFβR signaling domains with those of the PDGFαR resulted in varying degrees of vascular disease. This observation provides a framework for discussing the evolution of receptor tyrosine kinase functional specificity.
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