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Heterotrimeric GTP-binding proteins (G proteins) participate in cellular signaling and regulate a variety of physiological processes. Disruption of the gene encoding the G protein subunit α13 (Gα13) in mice impaired the ability of endothelial cells to develop into an organized vascular system, resulting in intrauterine death. In addition, Gα13 (−/−) embryonic fibroblasts showed greatly impaired migratory responses to thrombin. These results demonstrate that Gα13 participates in the regulation of cell movement in response to specific ligands, as well as in developmental angiogenesis.