Klages, Birgit and Brandt, Ursula and Simon, Melvin I. and Schultz, Günter and Offermanns, Stefan (1999) Activation of G(12)/G(13) results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. Journal of Cell Biology, 144 (4). pp. 745-754. ISSN 0021-9525 http://resolver.caltech.edu/CaltechAUTHORS:KLAjcb99
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Platelets respond to various stimuli with rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the alpha-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 G alpha(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 G alpha(q)-deficient platelets. Both MLC phosphorylation and shape change induced through G(12)/G(13) in the absence of G alpha(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.
|Additional Information:||© 1999 Rockefeller University Press. RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode. Received for publication 24 September 1998 and in revised form 19 January 1999. We thank Yoshitomi Pharmaceutical Industries, Ltd. for kindly providing us with Y-27632. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 366) and the Fonds der Chemischen Industrie.|
|Subject Keywords:||platelet; platelet shape change; G protein; Rho-kinase; myosin light chain phosphorylation|
|Usage Policy:||RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.|
|Deposited By:||Tony Diaz|
|Deposited On:||02 Dec 2008 19:27|
|Last Modified:||26 Dec 2012 10:30|
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