Galpha12 and Galpha13 stimulate Rho-dependent tyrosine phosphorylation of focal adhesion kinase, paxillin, and p130 Crk-associated substrate

We examined whether constitutively active mutants of the Galpha proteins Galpha12 and Galpha13, which together comprise the G12 subfamily of Galpha proteins, induce Rho-dependent tyrosine phosphorylation of the focal adhesion proteins p125 focal adhesion kinase, paxillin, and p130 Crk-associated sub...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-06, Vol.273 (23), p.14626
Main Authors: Needham, L K, Rozengurt, E
Format: Article
Language:English
Subjects:
Actins - physiology
ADP Ribose Transferases - pharmacology
Botulinum Toxins
Cell Adhesion Molecules - metabolism
Cell Line
Crk-Associated Substrate Protein
Cytochalasin D - pharmacology
Cytoskeletal Proteins - metabolism
Cytoskeleton - physiology
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
GTP-Binding Proteins - physiology
Humans
Intracellular Signaling Peptides and Proteins
Kidney - embryology
Paxillin
Phosphoproteins - metabolism
Phosphorylation
Phosphotyrosine - analysis
Protein-Serine-Threonine Kinases - metabolism
Protein-Tyrosine Kinases - metabolism
Proteins
Retinoblastoma-Like Protein p130
rho-Associated Kinases
Signal Transduction - physiology
Thrombin - pharmacology
Transfection - genetics
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Summary:We examined whether constitutively active mutants of the Galpha proteins Galpha12 and Galpha13, which together comprise the G12 subfamily of Galpha proteins, induce Rho-dependent tyrosine phosphorylation of the focal adhesion proteins p125 focal adhesion kinase, paxillin, and p130 Crk-associated substrate. We report that transient expression of the constitutively active mutants of Galpha12 or of Galpha13 in human embryonic kidney 293 cells stimulates tyrosine phosphorylation of a set of proteins of Mr of 110,000-130,000, 97,000, and 60,000-70,000. We identified p125 focal adhesion kinase, paxillin, and p130 Crk-associated substrate as prominent tyrosine-phosphorylated proteins in human embryonic kidney 293 cells expressing constitutively active Galpha12 and Galpha13. In common with the increased tyrosine phosphorylation of these proteins mediated by mitogens acting through heptahelical receptors, the Galpha12- and Galpha13-mediated increase in tyrosine phosphorylation is blocked by cytochalasin D, which specifically disrupts the actin cytoskeleton, and by the Clostridium botulinum C3 exoenzyme, which ADP-ribosylates and inactivates Rho. Our results support the hypothesis that Galpha12 and Galpha13 activate Rho and suggest that Galpha12 and Galpha13 may mediate the tyrosine phosphorylation of p125 focal adhesion kinase, paxillin, and p130 Crk-associated substrate.
ISSN:0021-9258