Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42.

Efficient chemotaxis requires directional sensing and cell polarization. We describe a signaling mechanism involving G beta gamma, PAK-associated guanine nucleotide exchange factor (PIX alpha), Cdc42, and p21-activated kinase (PAK) 1. This pathway is utilized by chemoattractants to regulate directional sensing and directional migration of myeloid cells. Our results suggest that ...
G beta gamma binds PAK1 and, via PAK-associated PIX alpha, activates Cdc42, which in turn activates PAK1. Thus, in this pathway, PAK1 is not only an effector for Cdc42, but it also functions as a scaffold protein required for Cdc42 activation. This G beta gamma-PAK1/PIX alpha/Cdc42 pathway is essential for the localization of F-actin formation to the leading edge, the exclusion of PTEN from the leading edge, directional sensing, and the persistent directional migration of chemotactic leukocytes. Although ligand-induced production of PIP(3) is not required for activation of this pathway, PIP(3) appears to localize the activation of Cdc42 by the pathway.
Mesh Terms:
Actins, Animals, COS Cells, Cell Polarity, Cercopithecus aethiops, Chemotaxis, Complement C5a, Enzyme Activation, Gene Expression Regulation, Enzymologic, Guanine Nucleotide Exchange Factors, Heterotrimeric GTP-Binding Proteins, Humans, Mice, Mice, Knockout, Models, Biological, Neutrophils, Phosphatidylinositol 3-Kinases, Protein-Serine-Threonine Kinases, Signal Transduction, Transfection, cdc42 GTP-Binding Protein
Cell
Date: Jul. 25, 2003
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