| Health / Medical Topics |
Rac1 Cell Motility Signaling Pathway
Rac-1 is a small G-protein in the Rho family that regulates cell motility in response to extracellular signals. Several changes in cytoskeletal structure and other aspects of cell structure are involved in cell motility. Rac-1 is activated by GEF factors, and repressed by GAPs. GEFs are guanine nucleotide exchange factors, including Trio and Vav. Sos-1 is involved in Ras signaling and also acts as a GEF for Rac to transduce signals between Ras and Rac. SWAP-70 is a Rac GEF that binds IP3 and transduces signals from tyrosine kinases to Rac to modulate the cytoskeleton and cause membrane ruffling. GAPs are GTPase- activating proteins. Rac stimulates the formation of actin-based structures such as filopodia and lamellipodia, while GAPs such as chimerin oppose the formation of these Rac dependent structures. Several different factors downstream of Rac act on cytoskeletal structure and other aspects of cell motility. Pak1 provides a direct link from Rac to cell motility through phosphorylation of the myosin light chain. Pak1 also phosphorylates and activates LIM kinase, which phosphorylates cofilin as one target. Cofilin stimulates actin depolymerization and changes in cell structure, and phosphorylation of cofilin by LIM kinase represses its activity. In neurons, Rac acts through the protein kinase cdk5 and p35 to phosphorylate and down regulate Pak1, increasing neuronal migration. Rac-1 also interacts with several other factors to regulate a variety of processes. Interaction of Por1 with Rac-1 is involved in membrane ruffling. WAVE is a member of the WASP family of proteins that regulate actin organization and that is involved in Rac signaling to cause membrane ruffling. Interaction of Rac-1 with MEKK1 integrates Rac signaling with pathways signaling through map kinases. (NCI Thesaurus/BIOCARTA)
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