Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603714
Title: The regulation of cytosolic phospholipase A2 in human platelets
Author: Hargreaves, P. G.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1997
Availability of Full Text:
Full text unavailable from EThOS. Please contact the current institution’s library for further details.
Abstract:
Human platelet cytosolic phospholipase A2 (cPLA2) mediates the release of arachidonic acid (AA) from membrane phospholipids. AA is the precursor for eicosanoids, such as thromboxane A2 (TxA2), which can contribute to platelet positive feedback. Collagen and ionomycin (a Ca2+ionophore) each provoked a release of AA from human platelets which was independent of TxA2 production and ADP secretion, but required at least cytosolic Ca2+ levels. Collagen-stimulated AA release and TxB2 production correlated with the rise in intracellular-free Ca2+ concentration ([Ca2+]i), and tyrosine phosphorylation. Ionomycin-stimulated AA release and TxB2 production correlated with PKC activation and tyrosine phosphorylation, but not with the rise in [Ca2+]i. Ro31-8220 (a PKC inhibitor) and genistein (a protein tyrosine kinase (PTK) inhibitor) were found to potentiate and suppress collagen-stimulated AA release respectively. Ro31-8220 and genistein each suppressed by 50%, and in combination almost abolished, ionomycin-stimulated AA release. Therefore, PKC is necessary for full AA release from ionomycin-stimulated platelets, but acts to suppress AA release in response to collagen. Furthermore, PTKs appear to mediate both collagen- and ionomycin-stimulated AA release. When platelets were activated by collagen, cPLA2 became phosphorylated upon tyrosine, and associated with several other phosphotyrosine-containing proteins. Moreover, cPLA2 was a good in vitro substrate for the PTK pp60c-src, which is abundant in platelets. To conclude, cPLA2 is likely regulated by both direct tyrosine phosphorylation, possibly mediated by pp60c-src, and indirect tyrosine phosphorylation of closely associated proteins.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.603714  DOI: Not available
Share: