2002
DOI: 10.1016/s1534-5807(01)00103-4
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An Allelic Series at the PDGFαR Locus Indicates Unequal Contributions of Distinct Signaling Pathways During Development

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 PDGFalpha receptor (PDGFalphaR) that selectively eliminate its capacity to activate PI3 kinase (alpha(PI3K)) or Src family kinases (alpha(Src)). The alpha(PI3K) mutation leads to neonatal lethality due to impaired signaling in many cell types, but the alpha(Src) mutation only affects oligodendrocyte development. A third knock… Show more

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Cited by 174 publications
(257 citation statements)
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“…The present study and that of Klinghoffer et al (2002) demonstrate OPC and oligodendrocyte formation in the absence of PDGFR␣ and formally raise the possibility that PDGFR␣ expression neither identifies all OPCs nor is obligate for OPC development. However, studies to date have not ruled out at least transient expression of PDGFR␣ in all OPC pools, and the contribution of "non-PDGFR␣"-expressing cells to oligodendrocyte formation remains unresolved.…”
Section: Opc Origins and Pdgfr␣supporting
confidence: 58%
See 1 more Smart Citation
“…The present study and that of Klinghoffer et al (2002) demonstrate OPC and oligodendrocyte formation in the absence of PDGFR␣ and formally raise the possibility that PDGFR␣ expression neither identifies all OPCs nor is obligate for OPC development. However, studies to date have not ruled out at least transient expression of PDGFR␣ in all OPC pools, and the contribution of "non-PDGFR␣"-expressing cells to oligodendrocyte formation remains unresolved.…”
Section: Opc Origins and Pdgfr␣supporting
confidence: 58%
“…Substitution studies in mice also demonstrate that the signaling domains of distinct PDGF receptors are qualitatively different. The signaling domain of PDGFR␣ cannot replace that of PDGFR␤ in development (Klinghoffer et al, 2001), and the signaling domains from FGFR1 or Drosophila Tor cannot replace that of PDGFR␣, although it can be replaced by PDGFR␤ (Klinghoffer et al, 2002;Hamilton et al, 2003). These results thus contrast with studies in Drosophila, in which the signaling domains of distinct RTKs can be functionally substituted during development (Dossenbach et al, 2001) and suggest that RTK signaling systems have gained both specificity and complexity with tissue specialization during metazoan evolution.…”
Section: Pdgfr␣ Signaling: Combinatorial Pathwaysmentioning
confidence: 84%
“…2 C-E). To determine whether the loss of PDGFRα in primary cilia attenuated PDGF-driven intracellular signaling, we measured the activation of PDGFRα and the induction of Akt phosphorylation, one of the effectors of PDGF signaling (38). Control osteoblasts stimulated with PDGF ligand [PDGF-AA] robustly activated PDGFRα and induced Akt phosphorylation, but Ift20:Wnt1-Cre osteoblasts did not ( Fig.…”
Section: Disruption Of Ift20 In Neural Crest Cells Results In Craniofmentioning
confidence: 99%
“…To date, studies have been reported of several receptors using knock-in mice in which the cytoplasmic tyrosine(s) of a receptor has been replaced with phenylalanine(s) (26)(27)(28)(29)(30). However, it is rare that the substitution of a single tyrosine of a receptor causes the same phenotype as the null mutant mice.…”
Section: Discussionmentioning
confidence: 99%