Tags

Type your tag names separated by a space and hit enter

Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-gamma2 is an early key event in FcgammaRIIA-mediated activation of human platelets.
J Biol Chem. 1998 Sep 18; 273(38):24314-21.JB

Abstract

Platelets express a single class of Fcgamma receptor (FcgammaRIIA), which is involved in heparin-associated thrombocytopenia and possibly in inflammation. FcgammaRIIA cross-linking induces platelet secretion and aggregation, together with a number of cellular events such as tyrosine phosphorylation, activation of phospholipase C-gamma2 (PLC-gamma2), and calcium signaling. Here, we show that in response to FcgammaRIIA cross-linking, phosphatidylinositol (3,4, 5)-trisphosphate (PtdIns(3,4,5)P3) is rapidly produced, whereas phosphatidylinositol (3,4)-bisphosphate accumulates more slowly, demonstrating a marked activation of phosphoinositide 3-kinase (PI 3-kinase). Inhibition of PI 3-kinase by wortmannin or LY294002 abolished platelet secretion and aggregation, as well as phospholipase C (PLC) activation, indicating a role of this lipid kinase in the early phase of platelet activation. Inhibition of PLCgamma2 was not related to its tyrosine phosphorylation state, since wortmannin actually suppressed its dephosphorylation, which requires platelet aggregation and integrin alphaIIb/beta3 engagement. In contrast, the stable association of PLCgamma2 to the membrane/cytoskeleton interface observed at early stage of platelet activation was fully abolished upon inhibition of PI 3-kinase. In addition, PLCgamma2 was able to preferentially interact in vitro with PtdIns(3,4,5)P3. Finally, exogenous PtdIns(3,4,5)P3 restored PLC activation in permeabilized platelets treated with wortmannin. We propose that PI 3-kinase and its product PtdIns(3,4,5)P3 play a key role in the activation and adequate location of PLCgamma2 induced by FcgammaRIIA cross-linking.

Authors+Show Affiliations

Institut Fédératif de Recherche en Immunologie Cellulaire et Moléculaire, Université Paul Sabatier and Centre Hospitalo-Universitaire de Toulouse, INSERM, Unité 326, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9733717

Citation

Gratacap, M P., et al. "Phosphatidylinositol 3,4,5-trisphosphate-dependent Stimulation of Phospholipase C-gamma2 Is an Early Key Event in FcgammaRIIA-mediated Activation of Human Platelets." The Journal of Biological Chemistry, vol. 273, no. 38, 1998, pp. 24314-21.
Gratacap MP, Payrastre B, Viala C, et al. Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-gamma2 is an early key event in FcgammaRIIA-mediated activation of human platelets. J Biol Chem. 1998;273(38):24314-21.
Gratacap, M. P., Payrastre, B., Viala, C., Mauco, G., Plantavid, M., & Chap, H. (1998). Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-gamma2 is an early key event in FcgammaRIIA-mediated activation of human platelets. The Journal of Biological Chemistry, 273(38), 24314-21.
Gratacap MP, et al. Phosphatidylinositol 3,4,5-trisphosphate-dependent Stimulation of Phospholipase C-gamma2 Is an Early Key Event in FcgammaRIIA-mediated Activation of Human Platelets. J Biol Chem. 1998 Sep 18;273(38):24314-21. PubMed PMID: 9733717.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-gamma2 is an early key event in FcgammaRIIA-mediated activation of human platelets. AU - Gratacap,M P, AU - Payrastre,B, AU - Viala,C, AU - Mauco,G, AU - Plantavid,M, AU - Chap,H, PY - 1998/9/12/pubmed PY - 1998/9/12/medline PY - 1998/9/12/entrez SP - 24314 EP - 21 JF - The Journal of biological chemistry JO - J Biol Chem VL - 273 IS - 38 N2 - Platelets express a single class of Fcgamma receptor (FcgammaRIIA), which is involved in heparin-associated thrombocytopenia and possibly in inflammation. FcgammaRIIA cross-linking induces platelet secretion and aggregation, together with a number of cellular events such as tyrosine phosphorylation, activation of phospholipase C-gamma2 (PLC-gamma2), and calcium signaling. Here, we show that in response to FcgammaRIIA cross-linking, phosphatidylinositol (3,4, 5)-trisphosphate (PtdIns(3,4,5)P3) is rapidly produced, whereas phosphatidylinositol (3,4)-bisphosphate accumulates more slowly, demonstrating a marked activation of phosphoinositide 3-kinase (PI 3-kinase). Inhibition of PI 3-kinase by wortmannin or LY294002 abolished platelet secretion and aggregation, as well as phospholipase C (PLC) activation, indicating a role of this lipid kinase in the early phase of platelet activation. Inhibition of PLCgamma2 was not related to its tyrosine phosphorylation state, since wortmannin actually suppressed its dephosphorylation, which requires platelet aggregation and integrin alphaIIb/beta3 engagement. In contrast, the stable association of PLCgamma2 to the membrane/cytoskeleton interface observed at early stage of platelet activation was fully abolished upon inhibition of PI 3-kinase. In addition, PLCgamma2 was able to preferentially interact in vitro with PtdIns(3,4,5)P3. Finally, exogenous PtdIns(3,4,5)P3 restored PLC activation in permeabilized platelets treated with wortmannin. We propose that PI 3-kinase and its product PtdIns(3,4,5)P3 play a key role in the activation and adequate location of PLCgamma2 induced by FcgammaRIIA cross-linking. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9733717/Phosphatidylinositol_345_trisphosphate_dependent_stimulation_of_phospholipase_C_gamma2_is_an_early_key_event_in_FcgammaRIIA_mediated_activation_of_human_platelets_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)60086-4 DB - PRIME DP - Unbound Medicine ER -