The C-terminal peptide of thrombospondin-1 stimulates distinct signaling pathways but induces an activation-independent agglutination of platelets and other cells.
A peptide from the C-terminal domain of thrombospondin-1 (4N1-1) has been proposed to stimulate platelet aggregation by a novel mechanism involving both an activation-independent agglutination and an activation-dependent, glycoprotein (GP) IIb/IIIa-mediated aggregation which involves GPVI signaling but does not involve CD47. The present study demonstrates that 4N1-1 stimulated a different pattern of signal transduction pathways than the GPVI agonist convulxin. Furthermore, 4N1-1-induced platelet aggregation was activation-independent and not dependent on GPVI or GPIIb/IIIa. Interestingly, 4N1-1 also stimulated activation-independent agglutination of different megakaryocytic and non-megakaryocytic cells. 4N1-1-induced cell agglutination but not platelet signaling was inhibited by anti-CD47 antibodies.
Voit
Simone
S
Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, Germany.
Udelhoven
Michael
M
Lill
Gereon
G
Aktas
Barsom
B
Nieswandt
Bernhard
B
Schrör
Karsten
K
Weber
Artur-Aron
AA
D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D001158:Arteries / Q000166:cytology; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D051928:CD47 Antigen; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019007:P-Selectin / Q000096:biosynthesis; D010455:Peptides; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases
D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D039661:Integrin beta3; D019007:P-Selectin; D010455:Peptides; D040201:Platelet Membrane Glycoprotein IIb; D019700:Thrombospondin 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium