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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Brandt, U. Simon, M. I. Schultz, G. Klages, B. Offermanns, S. |
| Description | Author Affiliation: Klages B ( Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 14195 Berlin, Germany.) |
| Abstract | Platelets respond to various stimuli with rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the α-subunit of the heterotrimeric G protein $G_{q}$ do not aggregate and degranulate but still undergo shape change after activation through $thromboxane-A_{2}(TXA_{2})$ or thrombin receptors. In contrast to thrombin, the $TXA_{2}$ mimetic U46619 led to the selective activation of $G_{12}$ and $G_{13}$ in $Gα_{q}-deficient$ platelets indicating that these G proteins mediate $TXA_{2}$ receptor-induced shape change. $TXA_{2}$ receptor-mediated activation of $G_{12}/G_{13}$ resulted in tyrosine phosphorylation of $pp72^{syk}$ and stimulation of $pp60^{c-src}$ as well as in phosphorylation of myosin light chain (MLC) in $Gα_{q}-deficient$ platelets. Both MLC phosphorylation and shape change induced through $G_{12}/G_{13}$ in the absence of $Gα_{q}$ were inhibited by the C3 exoenzyme from Clostridium botulinum, by the Rho-kinase inhibitor Y-27632 and by cAMP-analogue Sp-5,6-DCl-cBIMPS. These data indicate that $G_{12}/G_{13}$ couple receptors to tyrosine kinases as well as to the Rho/Rho-kinase–mediated regulation of MLC phosphorylation. We provide evidence that $G_{12}/G_{13}-mediated$ Rho/Rho-kinase–dependent regulation of MLC phosphorylation participates in receptor-induced platelet shape change. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 4 |
| Volume Number | 144 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1999-02-22 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Blood Platelets Cytology Metabolism GTP-Binding Proteins Blood GTPase-Activating Proteins Myosin Light Chains 15-Hydroxy-11 Alpha,9 Alpha-(epoxymethano)prosta-5,13-dienoic Acid Pharmacology Animals Drug Effects Cell Size Physiology GTP-Binding Protein Alpha Subunits, G12-G13 GTP-Binding Protein Alpha Subunits, Gq-G11 Deficiency Genetics Intracellular Signaling Peptides And Proteins Mice Microscopy, Electron, Scanning Phosphorylation Platelet Aggregation Protein-Serine-Threonine Kinases Receptors, Thromboxane Thrombin Rho-Associated Kinases Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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