title: Synthesis of phosphatidylinositol 3,4-bisphosphate but not phosphatidylinositol 3,4,5-trisphosphate is closely correlated with protein-tyrosine phosphorylation in thrombin-activated human platelets.
abstract: Synthesis of D-3-phosphorylated phosphoinositides and its correlation with protein-tyrosine phosphorylation were examined using human platelets. Thrombin stimulation of platelets resulted in time- and dose-dependent production of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), which is absent from resting platelets. In contrast, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) was detected in resting platelets, but remained unaffected by thrombin treatment. The production of PtdIns(3,4)P2 but not PtdIns(3,4,5)P3 was inhibited by pretreatment with staurosporine or dibutyryl cyclic adenosine monophosphate (dbcAMP). Protein-tyrosine phosphorylation, which is reportedly involved in generation of 3-phosphorylated phosphoinositides, was elicited in thrombin-activated platelets. The tyrosine phosphorylation was suppressed by pretreatment with staurosporine or dbcAMP. These observations suggest that synthesis of PtdIns(3,4)P2 but not PtdIns(3,4,5) P3 is closely correlated with protein-tyrosine phosphorylation in human platelets.
authors.affiliation: Department of Laboratory Medicine, Yamanashi Medical College, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Y
authors.initials: Y
authors.lastname: Ozaki
authors.forename: S
authors.initials: S
authors.lastname: Kume
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D007700:Kinetics; D010710:Phosphates / Q000097:blood; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D015539:Platelet Activation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000097:blood; D019311:Staurosporine; D013917:Thrombin / Q000494:pharmacology*; D014443:Tyrosine
chemical_list: D000470:Alkaloids; D010710:Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; C060980:phosphatidylinositol 3,4-diphosphate; D014443:Tyrosine; D003994:Bucladesine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine