|
||
J. Cell Biol.,
Volume 144, Number 4, February 22, 1999 745-754

* Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 14195 Berlin, Germany; and Platelets respond to various stimuli with
rapid changes in shape followed by aggregation and secretion of their granule contents. Platelets lacking the
Division of Biology, California Institute of Technology, Pasadena, California 91125
-subunit of the heterotrimeric G protein Gq do not aggregate and degranulate but still undergo shape change after activation through thromboxane-A2 (TXA2) or
thrombin receptors. In contrast to thrombin, the TXA2
mimetic U46619 led to the selective activation of G12
and G13 in G
q-deficient platelets indicating that these
G proteins mediate TXA2 receptor-induced shape
change. TXA2 receptor-mediated activation of G12/G13
resulted in tyrosine phosphorylation of pp72syk and
stimulation of pp60c-src as well as in phosphorylation of
myosin light chain (MLC) in G
q-deficient platelets.
Both MLC phosphorylation and shape change induced
through G12/G13 in the absence of G
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
G12/G13 couple receptors to tyrosine kinases as well as
to the Rho/Rho-kinase-mediated regulation of MLC
phosphorylation. We provide evidence that G12/G13-mediated Rho/Rho-kinase-dependent regulation of
MLC phosphorylation participates in receptor-induced platelet shape change.
This article has been cited by other articles:
|
|