Extracellular signal-regulated kinase (ERK) activation is required for GP Ibalpha-dependent endothelial cell migration.
The GP Ib complex can participate in endothelial cell (EC) migration on von Willebrand factor (vWF) or the mixed matrix of vWF and type I collagen (vWF/collagen). In this study, viper venom proteins alboaggregin (albo) A or B blocked GP Ibalpha, and echistatin inhibited alphavbeta3 binding. Albo A, B and echistatin inhibited EC migration on vWF and vWF/collagen. Albo B or the anti-GP Ibalpha monoclonal antibody (mAb) 1b1 did not affect the migration of smooth muscle cells or fibroblasts, which lack GP Ib. EC also migrate on albo A- or albo B-coated dishes. PD98059, which blocks ERK activation, abolished EC migration on vWF, vWF/collagen, collagen or albo B. Soluble albo A or 1b1 dramatically inhibited ERK activation during EC migration on vWF or albo B. Echistatin inhibited ERK activation on vWF and vitronectin (VN), but not albo B. Thus, in addition to alphavbeta3, EC GP Ibalpha initiates ERK activation, and regulates ERK-induced EC migration on vWF.
Lian
J
J
Cardeza Foundation for Hematologic Research, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
Marcinkiewicz
C
C
Niewiarowski
S
S
Beacham
D A
DA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000037:antagonists & inhibitors; D003435:Crotalid Venoms / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D019038:Platelet Glycoprotein GPIb-IX Complex; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; C112003:alboaggregin A; C112004:alboaggregin B; D014841:von Willebrand Factor; C057986:echistatin; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases