An allelic series at the PDGFαR locus indicates unequal contributions of distinct signaling pathways during development

Richard A. Klinghoffer, T. Guy Hamilton, Renée Hoch, Philippe Soriano

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

A central issue in signal transduction is the physiological contribution of different growth factor-initiated signaling pathways. We have generated knockin mice harboring mutations in the PDGFα receptor (PDGFαR) that selectively eliminate its capacity to activate P13 kinase (αP13K) or Src family kinases (αSrc). The αP13K mutation leads to neonatal lethality due to impaired signaling in many cell types, but the αSrc mutation only affects oligodendrocyte development. A third knockin line containing mutations that eliminate multiple docking sites does not increase the severity of the αP13K mutation. However, embryos with mutations in the P13K binding sites of both PDGFRs (α and β) recapitulate the PDGFαR null phenotype. Our results indicate that P13K has a predominant role in PDGF® signaling in vivo and that RTK-activated signaling pathways execute both specific and overlapping functions during mammalian development.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalDevelopmental Cell
Volume2
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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