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Defective platelet activation in Gα_q-deficient mice

Offermanns, Stefan and Toombs, Christopher F. and Hu, Yi-Hui and Simon, Melvin I. (1997) Defective platelet activation in Gα_q-deficient mice. Nature, 389 (6647). pp. 183-186. ISSN 0028-0836. doi:10.1038/38284.

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Platelets are small disc-shaped cell fragments which undergo a rapid transformation when they encounter vascular damage. They become more spherical and extrude pseudopodia, their fibrinogen receptors are activated, causing them to aggregate, they release their granule contents, and eventually form a plug which is responsible for primary haemostasis. Activation of platelets is also implicated in the pathogenesis of unstable angina, myocardial infarction and stroke. Here we show that platelets from mice deficient in the α-subunit of the heterotrimeric guanine-nucleotide-binding protein Gq are unresponsive to a variety of physiological platelet activators. As a result, G α_q-deficient mice have increased bleeding times and are protected from collagen and adrenaline-induced thromboembolism. We conclude that G α_q is essential for the signalling processes used by different platelet activators and that it cannot be replaced by G α_i or the βγ subunits of the heterotrimeric G proteins. G α_q may thus be a new target for drugs designed to block the activation of platelets.

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Additional Information:© 1997 Macmillan Publishers Ltd. Received 6 May; accepted 11 June 1997. We thank S. R. Coughlin and H. Ishihara for advice, and V. Mancino, H. Li, S. Pease and J. Silva for technical help. S.O. was a recipient of a fellowship from the Deutsche Forschungsgemeinschaft and the Guenther Foundation. Supported by a grant from the NIH to M.I.S.
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Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Guenther FoundationUNSPECIFIED
Issue or Number:6647
Record Number:CaltechAUTHORS:20150616-145757001
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58290
Deposited By: Tony Diaz
Deposited On:16 Jun 2015 23:24
Last Modified:10 Nov 2021 22:02

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