Naslov
A type II phosphoinositide 3-kinase is stimulated via activated integrin in platelets. A source of phosphatidylinositol 3-phosphate

Autori
Zhang, J. ; Banfić, Hrvoje ; Straforini, F. ; Tosi, L. ; Volinia, S. ; Rittenhouse, S.E.

Izvornik
The Journal of biological chemistry (0021-9258) 273 (1998), 23; 14081-14084

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
phosphoinositide 3-kinase; integrin; platelets; phosphatidylinositol 3-phosphate

Sažetak
We have observed that aggregation of human platelets, caused by activation of integrin alphaIIb beta3 and its consequent binding of fibrinogen, stimulates a novel pathway for synthesis of phosphatidylinositol 3, 4bisphosphate, thereby activating protein kinase B/Akt. Such synthesis depends upon both the generation of phosphatidylinositol 3-phosphate (PtdIns3P), which is sensitive to wortmannin (IC50 7 nM) and calpain inhibitors, and the phosphorylation of PtdIns3P by PtdIns3P 4-kinase. We now report that a recently characterized C2 domain-containing phosphoinositide 3-kinase isoform (HsC2-PI3K) is present in platelets and a leukemic cell line (CHRF-288) derived from megakaryoblasts, and is likely to be responsible for the stimulated synthesis of PtdIns3P observed in platelets. HsC2-PI3K, identifiable by Western blotting and immunoprecipitatable activity, is sensitive to wortmannin (IC50 6-10 nM), requires Mg2+, and shows strong preference for PtdIns over PtdIns4P or phosphatidylinositol 4, 5-bisphosphate as substrate. HsC2-PI3K is activated severalfold when platelets aggregate in an alphaIIb beta3-dependent manner or when platelet or CHRF-288 lysates are incubated with Ca2+. Activation is prevented by calpain inhibitors. CHRF-288, which cannot undergo activation of alphaIIb beta3 and thereby aggregate in response to platelet agonists, do not generate PtdIns3P or activate HsC2-PI3K under conditions that stimulate other phosphoinositide 3-kinases. HsC2-PI3K may thus be an important effector for integrin-dependent signaling.

Izvorni jezik
Engleski

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