G-Protein Coupled Receptors (GPCR) sense extracellular signals and activate different Guanine nucleotide binding proteins (G-proteins) that have alpha, beta and gamma subunits. Upon activation, the alpha subunit of G-proteins dissociates from beta-gamma and the both are then free to regulate downstream effectors. Serine/threonine-protein kinase PAK 1 binds with Rho guanine nucleotide exchange factor 6 (ARHGEF6, PIX-Alpha) in the cytosol and is subsequently translocated by the G-protein beta-gamma complex to the plasma membrane. Here, ARHGEF6 activates Cell division control protein 42 homolog (CDC42) by acting as a GEF. Once active, CDC42 can facilitate the activation of PAK1. At this stage the whole complex dissociates to release the active CDC42 and active PAK1. CDC42 is known to be involved in epithelial cell polarization processes. PAK1 plays an important role in cytoskeleton dynamics and cell adhesion.
Wu, Y, Li, Z, Mo, Z, Smrcka, AV, Huang, CK, Liu, B, Lu, W, Wu, G, Wu, D, Li, L, Liu, M, Hannigan, M
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