D3 phosphoinositides and outside-in integrin signaling by glycoprotein IIb-IIIa mediate platelet actin assembly and filopodial extension induced by phorbol 12-myristate 13-acetate.

Details

Serval ID
serval:BIB_5468
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
D3 phosphoinositides and outside-in integrin signaling by glycoprotein IIb-IIIa mediate platelet actin assembly and filopodial extension induced by phorbol 12-myristate 13-acetate.
Journal
Journal of Biological Chemistry
Author(s)
Hartwig J.H., Kung S., Kovacsovics T., Janmey P.A., Cantley L.C., Stossel T.P., Toker A.
ISSN
0021-9258
Publication state
Published
Issued date
1996
Volume
271
Number
51
Pages
32986-32993
Language
english
Abstract
Phorbol 12-myristate 13-acetate (PMA) uncaps a small number of the fast-growing (barbed) ends of actin filaments, thereby eliciting slow actin assembly and extension of filopodia in human blood platelets. These reactions, which also occur in response to immunologic perturbation of the integrin glycoprotein (GP) IIb-IIIa, are sensitive to the phosphoinositide 3-kinase inhibitor wortmannin. Platelets deficient in GPIIb-IIIa integrins or with GPIIb-IIIa function inhibited by calcium chelation or the peptide RGDS have diminished PMA responsiveness. The effects of PMA contrast with thrombin receptor stimulation by >/=5 microM thrombin receptor-activating peptide (TRAP), which causes rapid and massive wortmannin-insensitive actin assembly and lamellar and filopodial extension. However, we show here that wortmannin can inhibit filopod formation if the thrombin receptor is ligated using suboptimal doses (<1 microM) of TRAP. Phosphatidylinositol 3,4-bisphosphate inhibits actin filament severing and capping by human gelsolin in vitro. The findings implicate D3 polyphosphoinositides and integrin signaling in PMA-mediated platelet stimulation and implicate D3 containing phosphoinositides generated in response to protein kinase C activation and GPIIb-IIIa signaling as late-acting intermediates leading to filopodial actin assembly.
Keywords
1-Phosphatidylinositol 3-Kinase, Actins/metabolism, Androstadienes/pharmacology, Blood Platelets/physiology, Blood Platelets/ultrastructure, Cytochalasin B/pharmacology, Enzyme Inhibitors/pharmacology, Gelsolin/metabolism, Humans, Microfilaments/drug effects, Microfilaments/ultrastructure, Oligopeptides/pharmacology, Phosphatidylinositol 4,5-Diphosphate/physiology, Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors, Platelet Glycoprotein GPIIb-IIIa Complex/physiology, Receptors, Thrombin/physiology, Signal Transduction, Tetradecanoylphorbol Acetate/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2007 12:41
Last modification date
20/08/2019 14:09
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