Thrombopoietin potentiates agonist-stimulated activation of p38 mitogen-activated protein kinase in human platelets.
Thrombopoietin (TPO) plays a crucial role in megakaryocyte differentiation and platelet production. c-Mpl, a receptor for TPO, is also expressed in terminally differentiated platelets. We investigated the effects of TPO on activation of p38 mitogen-activated protein kinase in human platelets. Thrombin, a thrombin receptor agonist peptide, a thromboxane A(2) analogue, collagen, crosslinking the glycoprotein VI, ADP, and epinephrine, but not phorbol 12, 13-dibutyrate activated p38. TPO did not activate p38 by itself, whereas TPO pretreatment potentiated the agonist-induced activation of p38. TPO did not promote phosphorylation of Hsp27 and cytosolic phospholipase A(2) by itself, but enhanced thrombin-induced phosphorylation of them. The specific p38 inhibitor SB203580 strongly inhibited such phosphorylation. Thus, TPO possesses the priming effect on p38 activation in human platelets and could affect platelet functions through the p38 pathway.
Ezumi
Y
Y
Clinical Sciences for Pathological Organs, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
Nishida
E
E
Uchiyama
T
T
Takayama
H
H
D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000097:blood*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000097:blood; D010741:Phospholipases A / Q000097:blood; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000097:blood; D011725:Pyridines / Q000494:pharmacology; D018179:Receptors, Thrombin / Q000819:agonists* / Q000502:physiology; D013917:Thrombin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D007093:Imidazoles; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011725:Pyridines; D018179:Receptors, Thrombin; D019000:Phosphotyrosine; D013926:Thrombopoietin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D013917:Thrombin; C093642:SB 203580