Activation of Rap1B by G(i) family members in platelets.

Activation of Rap1B by G(i) family members in platelets. Research Abstract Details 

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Activation of Rap1B by G(i) family members in platelets. Abstract Text:

It has become increasingly appreciated that receptors coupled to G(alpha)(i) family members can stimulate platelet aggregation, but the mechanism for this has remained unclear. One possible mediator is the small GTPase, Rap1, which has been shown to contribute to integrin activation in several cell lines and to be activated by a calcium-dependent mechanism in platelets. Here, we demonstrate that Rap1 is also activated by G(alpha)(i) family members in platelets. First, we show that platelets from mice lacking the G(alpha)(i) family member G(alpha)(z) (which couples to the alpha(2A) adrenergic receptor) are deficient in epinephrine-stimulated Rap1 activation. We also show that platelets from mice lacking G(alpha)(i2), which couples to the ADP receptor, P2Y12, exhibit reduced Rap1 activation in response to ADP. In contrast, platelets from mice that lack G(alpha)(q) show no decrease in the ability to activate Rap1 in response to epinephrine but show a partial reduction in ADP-stimulated Rap1 activation. This result, combined with studies of human platelets treated with ADP receptor-selective inhibitors, indicates that ADP-stimulated Rap1 activation in human platelets is dependent on both the G(alpha)(i)-coupled P2Y12 receptor and the G(alpha)(q)-coupled P2Y1 receptor. G(alpha)(i)-dependent activation of Rap1 in platelets does not appear to be mediated by enhanced intracellular calcium release because no increase in intracellular calcium concentration was detected in response to epinephrine and because the calcium response to ADP was not diminished in platelets from the G(alpha)(i2)-/- mouse. Finally, using human platelets treated with selective inhibitors of phosphatidylinositol 3-kinase (PI3K) and mouse platelets selectively lacking the G(beta)(gamma)-activated form of his enzyme (PI3Kgamma), we show that G(i)-mediated Rap1 activation is PI3K-dependent. In summary, activation of Rap1 can be stimulated by G(alpha)(i)- and PI3K-dependent mechanisms in platelets and by G(q)- and Ca(2+)-dependent mechanisms, both of which may play a role in promoting platelet activation.

Activation of Rap1B by G(i) family members in platelets. Publishing Authors By Initials

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Activation of Rap1B by G(i) family members in platelets. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 277

Page Numbers: 23382-90

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 22

MONTH: 04

YEAR: 2002

Activation of Rap1B by G(i) family members in platelets. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Activation of Rap1B by G(i) family members in platelets. Keywords Mesh Terms:

KEYWORDS: rap1 GTP-Binding Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Activation of Rap1B by G(i) family members in platelets. Information

Substance Name: Adenylate Cyclase

Registry Number: EC 4.6.1.1

Grant and Affiliation Information for Activation of Rap1B by G(i) family members in platelets.

AFFILIATION: Department of Medicine, Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-45181

ACRONYM: HL

MEDLINETA: J Biol Chem

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