Identification of functional VEGF receptors on human platelets.
Platelets secrete platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) upon stimulation. We have demonstrated that platelets have functionally active PDGF alpha-receptors, a transmembrane tyrosine kinase involved in negative feedback regulation. Here we demonstrate the presence of the related VEGF receptors fms-like tyrosine kinase-1 and kinase-insert domain region on human platelets. VEGF itself did not cause platelet aggregation. However, addition of exogenous VEGF to SFRLLN or thrombin-stimulated platelets potentiated platelet aggregation. Moreover, thrombin-induced phosphoinositide 3-kinase and mitogen-activated protein kinase activity were enhanced in the presence of VEGF.
Selheim
Frode
F
Department of Biochemistry and Molecular Biology, University of Bergen, Bergen, Norway. frode.selheim@pki.uib.no
Holmsen
Holm
H
Vassbotn
Flemming S
FS
D001792:Blood Platelets / Q000187:drug effects*; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015539:Platelet Activation; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification*; D020794:Receptor Protein-Tyrosine Kinases / Q000302:isolation & purification*; D017978:Receptors, Growth Factor / Q000302:isolation & purification*; D018179:Receptors, Thrombin / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D018179:Receptors, Thrombin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C082835:thrombin receptor peptide (42-47); D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin