Title |
Protein kinase C Mediates Translocation of Type II Phosphatidylinositol 5-Phosphate 4-Kinase Required for Platelet α-Granule Secretion*
|
---|---|
Published in |
Journal of Biological Chemistry, December 2002
|
DOI | 10.1074/jbc.m206493200 |
Pubmed ID | |
Authors |
Nataliya Rozenvayn, Robert Flaumenhaft |
Abstract |
To better understand the molecular mechanisms of platelet granule secretion, we have evaluated the role of type II phosphatidylinositol (PtdIns) 5-phosphate 4-kinase in agonist-induced platelet alpha-granule secretion. SFLLRN-stimulated alpha-granule secretion from SL-O-permeabilized platelets was inhibited by either antibodies directed at type II PtdIns 5-phosphate 4-kinase or by a kinase-impaired point mutant of type IIbeta PtdIns 5-phosphate 4-kinase. In contrast, recombinant type IIbeta PtdIns 5-phosphate 4-kinase augmented SFLLRN-stimulated alpha-granule secretion from SL-O-permeabilized platelets. SFLLRN-stimulated alpha-granule secretion was inhibited by a protein kinase C-specific inhibitor peptide or bisindolylmaleimide I. Phorbol 12-myristate 13-acetate-stimulated alpha-granule secretion was inhibited by anti-type II PtdIns 5-phosphate 4-kinase antibodies or the kinase-impaired point mutant of type IIbeta PtdIns 5-phosphate 4-kinase and augmented by recombinant type IIbeta PtdIns 5-phosphate 4-kinase. Immunoblot analysis demonstrated that type II PtdIns 5-phosphate 4-kinase remained associated with SL-O-permeabilized platelets when incubated in the presence, but not the absence, of SFLLRN. This SFLLRN-induced translocation of type II PtdIns 5-phosphate 4-kinase was blocked by either the protein kinase C-specific inhibitor peptide or bisindolylmaleimide I. In addition to stimulating alpha-granule secretion, both SFLLRN and PMA enhanced the association of a fluorescein isothiocyanate-labeled peptide derived from the PtdIns (4,5)P(2)-binding domain of gelsolin to permeabilized platelets. Agonist-induced recruitment of the PtdIns (4,5)P(2)-binding domain was inhibited by neomycin, bisindolylmaleimide I, and anti-type II PtdIns 5-phosphate 4-kinase antibody. These results suggest a mechanism whereby protein kinase C-mediated translocation of type II PtdIns 5-phosphate 4-kinase leads to the recruitment of PtdIns (4,5)P(2)-binding proteins. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 4% |
Greece | 1 | 4% |
Unknown | 22 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 4 | 17% |
Researcher | 4 | 17% |
Student > Bachelor | 3 | 13% |
Professor | 3 | 13% |
Professor > Associate Professor | 3 | 13% |
Other | 3 | 13% |
Unknown | 4 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 13 | 54% |
Biochemistry, Genetics and Molecular Biology | 2 | 8% |
Medicine and Dentistry | 2 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Engineering | 1 | 4% |
Other | 0 | 0% |
Unknown | 5 | 21% |