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Pregled bibliografske jedinice broj: 17550

Biphasic activation of PKBalpha/Akt in platelets - Evidence for stimulation both by phosphatidylinositol 3, 4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3, 4, 5-trisphosphate


Banfić, Hrvoje; Dowens, C.P.; Rittenhouse, S.E.
Biphasic activation of PKBalpha/Akt in platelets - Evidence for stimulation both by phosphatidylinositol 3, 4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3, 4, 5-trisphosphate // Journal of Biological Chemistry, 273 (1998), 19; 11630-11637 (međunarodna recenzija, članak, znanstveni)


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Naslov
Biphasic activation of PKBalpha/Akt in platelets - Evidence for stimulation both by phosphatidylinositol 3, 4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3, 4, 5-trisphosphate

Autori
Banfić, Hrvoje ; Dowens, C.P. ; Rittenhouse, S.E.

Izvornik
Journal of Biological Chemistry (0021-9258) 273 (1998), 19; 11630-11637

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

Ključne riječi
protein kinase Balfa/Akt; platelets; polyphosphoinositides

Sažetak
Stimulation of platelet thrombin receptors or protein kinase C causes fibrinogen-dependent aggregation that is a function of integrin alphaIIb beta3 activation. Such platelets rapidly and transiently form phosphatidylinositol 3, 4, 5-trisphosphate (PtdIns(3, 4, 5)P3) and a small amount of phosphatidylinositol 3, 4-bisphosphate (PtdIns(3, 4)P2). After aggregation, a larger amount of PtdIns(3, 4)P2 is generated. We report that this latter PtdIns(3, 4)P2 arises largely through wortmannin-inhibitable generation of PtdIns3P and then phosphorylation by PtdIns3P 4-kinase (PtdIns3P 4-K), a novel pathway apparently contingent upon the activation of the Ca2+-dependent protease calpain. Elevation of cytosolic Ca2+ by ionophore, without integrin/ligand binding, is insufficient to activate the pathway. PtdIns3P 4-K is not the recently described "PIP5KIIalpha." Cytoskeletal activities of phosphatidylinositol 3-kinase and PtdIns3P 4-K increase after aggregation. Prior to aggregation, PtdIns3P 4-K can be regulated negatively by the beta gamma subunit of heterotrimeric GTP-binding protein. After aggregation, PtdIns3P 4-K calpain-dependently loses its susceptibility to Gbeta gamma and is, in addition, activated. Both PtdIns(3, 4, 5)P3 and PtdIns(3, 4)P2 have been shown to stimulate PKBalpha/Akt phosphorylation and activation by phosphoinositide-dependent kinase 1. We find that activation of PKBalpha/Akt in platelets is phosphorylation-dependent and biphasic ; the initial phase is PtdIns(3, 4, 5)P3-dependent and more efficient, whereas the second phase depends upon PtdIns(3, 4)P2 generated after aggregation. There is thus potential for both pre- and post-aggregation-dependent signaling by PKBalpha/Akt.

Izvorni jezik
Engleski



POVEZANOST RADA


Projekti:
108013

Ustanove:
Medicinski fakultet, Zagreb

Profili:

Avatar Url Hrvoje Banfić (autor)

Citiraj ovu publikaciju:

Banfić, Hrvoje; Dowens, C.P.; Rittenhouse, S.E.
Biphasic activation of PKBalpha/Akt in platelets - Evidence for stimulation both by phosphatidylinositol 3, 4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3, 4, 5-trisphosphate // Journal of Biological Chemistry, 273 (1998), 19; 11630-11637 (međunarodna recenzija, članak, znanstveni)
Banfić, H., Dowens, C. & Rittenhouse, S. (1998) Biphasic activation of PKBalpha/Akt in platelets - Evidence for stimulation both by phosphatidylinositol 3, 4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3, 4, 5-trisphosphate. Journal of Biological Chemistry, 273 (19), 11630-11637.
@article{article, author = {Banfi\'{c}, Hrvoje and Dowens, C.P. and Rittenhouse, S.E.}, year = {1998}, pages = {11630-11637}, keywords = {protein kinase Balfa/Akt, platelets, polyphosphoinositides}, journal = {Journal of Biological Chemistry}, volume = {273}, number = {19}, issn = {0021-9258}, title = {Biphasic activation of PKBalpha/Akt in platelets - Evidence for stimulation both by phosphatidylinositol 3, 4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3, 4, 5-trisphosphate}, keyword = {protein kinase Balfa/Akt, platelets, polyphosphoinositides} }
@article{article, author = {Banfi\'{c}, Hrvoje and Dowens, C.P. and Rittenhouse, S.E.}, year = {1998}, pages = {11630-11637}, keywords = {protein kinase Balfa/Akt, platelets, polyphosphoinositides}, journal = {Journal of Biological Chemistry}, volume = {273}, number = {19}, issn = {0021-9258}, title = {Biphasic activation of PKBalpha/Akt in platelets - Evidence for stimulation both by phosphatidylinositol 3, 4-bisphosphate, produced via a novel pathway, and by phosphatidylinositol 3, 4, 5-trisphosphate}, keyword = {protein kinase Balfa/Akt, platelets, polyphosphoinositides} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE





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