Alterations in thrombin-induced protein tyrosine phosphorylation of platelets from patients with chronic myelogenous leukemia.
Thrombin is known to stimulate platelet protein tyrosine kinase (PTK). We studied thrombin-induced tyrosine-specific protein phosphorylation in normal platelets and those from patients with chronic myelogenous leukemia (CML) and other myeloproliferative disorders (MPD) using immunoblotting with antiphosphotyrosine (anti-P-Tyr) antibody. In resting platelets, two major phosphotyrosyl (P-Tyr) proteins with molecular masses of 120 kDa (p120) and 60 kDa (p60) were consistently detected both in normal subjects and in CML and other MPD patients. In addition to these P-Tyr proteins, a 36 kDa protein (p36) was predominantly phosphorylated only in CML platelets, using antilipocortin II antibody, we identified this p36 protein as lipocortin. Thrombin enhanced the tyrosine phosphorylation of p120 and p60, not only in normal platelets, but also in CML platelets, although the response was more delayed and the duration was shorter in CML platelets than those in normal platelets. Interestingly, decreased thrombin-induced aggregation was associated with a transient stimulation of p36 phosphorylation in CML platelets. These results suggest that the tyrosine phosphorylation of p36, which was probably identical to lipocortin, inhibits thrombin-induced platelet aggregation through anti-phospholipase A2 (anti-PLA2) activity.
Shibata
K
K
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nishimura
J
J
Yufu
Y
Y
Nawata
H
H
D017302:Annexins; D001792:Blood Platelets / Q000201:enzymology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology*; D009196:Myeloproliferative Disorders / Q000201:enzymology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology*
D017302:Annexins; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin