Csk, a Critical Link of G Protein Signals to Actin Cytoskeletal Reorganization

• Published in: Developmental cell Vol. 2; no. 6; pp. 733 - 744
• Main Authors: Lowry, William E., Huang, Jianyun, Ma, Yong-Chao, Ali, Shariq, Wang, Dongxia, Williams, Daniel M., Okada, Masato, Cole, Philip A., Huang, Xin-Yun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2002
• Subjects: 3T3 Cells; Actins - drug effects; Actins - physiology; Animals; Biological Transport; Catalysis; Cell Line; Cell Membrane - physiology; Cytoskeleton - physiology; Enzyme Activation; Fibroblasts - enzymology; Heterotrimeric GTP-Binding Proteins - genetics; Heterotrimeric GTP-Binding Proteins - metabolism; Heterotrimeric GTP-Binding Proteins - pharmacology; Humans; Mice; Mice, Knockout; Mutation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins - metabolism; Receptors, Cell Surface - metabolism; Receptors, Opioid - metabolism; Recombinant Fusion Proteins - metabolism; Signal Transduction; src-Family Kinases - deficiency; src-Family Kinases - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(02)00175-2

Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient mouse embryonic fibroblast cells, G protein (Gβγ, Gα 12, Gα 13, and Gα q)-induced, and G protein-coupled receptor-induced, actin stress fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent cells restored the G protein-induced actin stress fiber formation. Chemical rescue experiments with catalytic mutants of Csk demonstrated that the catalytic activity of Csk was required for this process. Furthermore, we uncovered that Gβγ can both translocate Csk to the plasma membrane and directly increase Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk plays a critical role in mediating G protein signals to actin cytoskeletal reorganization.