Linked Life Data

8199204

Source:http://linkedlifedata.com/resource/pubmed/id/8199204

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-7-7
pubmed:abstractText
To elucidate the mechanism involving synthesis of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), which is the main species of 3-phosphorylated phosphoinositides in activated blood platelets, we observed a correlation among protein-tyrosine phosphorylation, protein kinase C (PKC) activation, and PtdIns(3,4)P2 synthesis in these anucleate cells. Thrombin (1 U/ml) elicited marked protein-tyrosine phosphorylation, PKC activation, and PtdIns(3,4)P2 synthesis. In contrast, 1 microM 12-O-tetrade-canoylphorbol 13-acetate barely induced tyrosine phosphorylation and PtdIns(3,4)P2 synthesis although it strongly activated PKC. A variety of kinase inhibitors were tested for their ability to inhibit the thrombin effects. Both staurosporine and tyrphostin inhibited thrombin-stimulated tyrosine phosphorylation and PtdIns(3,4)P2 synthesis. H-7, which specifically, although weakly, inhibited PKC activation, had no effect on tyrosine phosphorylation and PtdIns(3,4)P2 production. Among the various kinase inhibitors tested, staurosporine was the most potent inhibitor of protein tyrosine phosphorylation and PtdIns(3,4)P2 synthesis, and there was a good correlation of the inhibition between these two parameters, although it also inhibited PKC activation. To examine the involvement of PtdIns 3-kinase, which is believed to play an important role in 3-phosphorylated phosphoinositide synthesis, we studied tyrosine phosphorylation and the association with tyrosine-phosphorylated proteins of the p85 alpha subunit of PtdIns 3-kinase in thrombin-stimulated platelets. We did not detect tyrosine-phosphorylated protein by Western blotting where p85 alpha was located. Similarly, when platelet lysates were precipitated with anti-p85 alpha antibodies and then blotted with anti-phosphotyrosine antibodies, tyrosine-phosphorylated p85 alpha was undetectable. Furthermore, when the cell lysates were precipitated with anti-phosphotyrosine antibodies, no p85 alpha was found in the immunoprecipitates. These results show that PtdIns(3,4)P2 synthesis in stimulated platelets is mediated by tyrosine phosphorylation, as it is in proliferating cells, but the p85 alpha subunit of PtdIns 3-kinase may not be a target for tyrosine kinases and that staurosporine, though non-specific, would be a useful tool for elucidating signal transduction involving D-3-phosphorylated phosphoinositide generation and protein-tyrosine phosphorylation in blood platelets.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp..., http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids, http://linkedlifedata.com/resource/pubmed/chemical/Catechols, http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines, http://linkedlifedata.com/resource/pubmed/chemical/Nitriles, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol Phosphates, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., http://linkedlifedata.com/resource/pubmed/chemical/Piperazines, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Thrombin, http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins, http://linkedlifedata.com/resource/pubmed/chemical/phosphatidylinositol 3,4-diphosphate, http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin 47
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
1212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
337-44
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:8199204-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, pubmed-meshheading:8199204-Alkaloids, pubmed-meshheading:8199204-Blood Platelets, pubmed-meshheading:8199204-Catechols, pubmed-meshheading:8199204-Enzyme Activation, pubmed-meshheading:8199204-Humans, pubmed-meshheading:8199204-Isoquinolines, pubmed-meshheading:8199204-Nitriles, pubmed-meshheading:8199204-Phosphatidylinositol 3-Kinases, pubmed-meshheading:8199204-Phosphatidylinositol Phosphates, pubmed-meshheading:8199204-Phosphorylation, pubmed-meshheading:8199204-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:8199204-Piperazines, pubmed-meshheading:8199204-Protein Kinase C, pubmed-meshheading:8199204-Protein-Tyrosine Kinases, pubmed-meshheading:8199204-Staurosporine, pubmed-meshheading:8199204-Tetradecanoylphorbol Acetate, pubmed-meshheading:8199204-Thrombin, pubmed-meshheading:8199204-Tyrphostins
pubmed:year
1994
pubmed:articleTitle
Synthesis of phosphatidylinositol 3,4-bisphosphate is regulated by protein-tyrosine phosphorylation but the p85 alpha subunit of phosphatidylinositol 3-kinase may not be a target for tyrosine kinases in thrombin-stimulated human platelets.
pubmed:affiliation
Department of Laboratory Medicine, Yamanashi Medical College, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't