The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation

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Abstract
The Ras signalling pathway has major roles in normal cell function and oncogenesis. C3G is a guanine nucleotide exchange factor for members of the Ras family of GTPases. We generated a mouse strain with a hypomorphicC3G allele. C3Ggt/gt mutant embryos died of vascular defects around E11.5 due to haemorrhage and vascular integrity defects. Vascular supporting cells did not develop appropriately. C3G-deficient fibroblasts responded to PDGF-BB abnormally, exhibited cell adhesion defects and lacked paxillin and integrin-β1-positive cell adhesions. In contrast, integrin-β3-positive cell adhesions formed normally. These results show that C3G is required for (1) vascular myogenesis,(2) the formation of paxillin- and integrin β1-positive, but not integrinβ3-positive, cell adhesions and (3) normal response to PDGF, necessary for vascular myogenesis.