Csk, a critical link of g protein signals to actin cytoskeletal reorganization.
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 (Gbetagamma, Galpha(12), Galpha(13), and Galpha(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 Gbetagamma 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.
Lowry
William E
WE
Department of Physiology, Cornell University, Weill Medical College, New York, New York 10021, USA.
Huang
Jianyun
J
Ma
Yong-Chao
YC
Ali
Shariq
S
Wang
Dongxia
D
Williams
Daniel M
DM
Okada
Masato
M
Cole
Philip A
PA
Huang
Xin-Yun
XY
D016475:3T3 Cells; D000199:Actins / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D000081247:CSK Tyrosine-Protein Kinase; D002384:Catalysis; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000172:deficiency / Q000378:metabolism*; D000094942:Nociceptin Receptor
D000199:Actins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011957:Receptors, Opioid; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D020962:Heterotrimeric GTP-Binding Proteins; D000094942:Nociceptin Receptor