Tyrphostin 23 blocks phosphorylation of p42 but not p38 mitogen-activated protein kinase by zooxanthellatoxin-A.
Zooxanthellatoxin-A isolated from a symbiotic dinoflagellate, caused aggregation in rabbit platelets that was inhibited by genistein (50 microM) and tyrphostin 23 (500 microM). Zooxanthellatoxin-A increased tyrosine phosphorylation of 42-kDa proteins which were identified as p42 and p38 mitogen-activated protein kinase (MAPK) by immunoprecipitation. Tyrphostin 23 inhibited the tyrosine phosphorylation of p42 MAPK but not p38 MAPK. In contrast, genistein abolished zooxanthellatoxin-A-induced tyrosine phosphorylation of both p42 and p38 MAPK. The results suggest that tyrphostin 23 selectively inhibits tyrosine phosphorylation of p42 MAPK. The p38 MAPK tyrosine phosphorylation is not involved in zooxanthellatoxin-A-induced platelet aggregation.
Rho
M C
MC
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Nakahata
N
N
Nakamura
H
H
Murai
A
A
Ohizumi
Y
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D011090:Polyenes / Q000494:pharmacology*; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins; D048051:p38 Mitogen-Activated Protein Kinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002396:Catechols; D004791:Enzyme Inhibitors; D007529:Isoflavones; D008387:Marine Toxins; D009570:Nitriles; D011090:Polyenes; D020032:Tyrphostins; C081400:zooxanthellatoxin A; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C060641:tyrphostin A23; D007213:Indomethacin