The C-terminal peptide of thrombospondin-1 stimulates distinct signaling pathways but induces an activation-independent agglutination of platelets and other cells

FEBS Lett. 2003 Jun 5;544(1-3):240-5. doi: 10.1016/s0014-5793(03)00472-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / metabolism
  • Arteries / cytology
  • Blood Platelets / metabolism*
  • Blotting, Western
  • CD47 Antigen
  • Calcium / metabolism
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Integrin beta3 / metabolism
  • Megakaryocytes / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • P-Selectin / biosynthesis
  • Peptides
  • Platelet Membrane Glycoprotein IIb / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Signal Transduction
  • Thrombospondin 1 / chemistry*
  • Tumor Cells, Cultured
  • U937 Cells
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Antigens, CD
  • CD47 Antigen
  • CD47 protein, human
  • Carrier Proteins
  • Integrin beta3
  • P-Selectin
  • Peptides
  • Platelet Membrane Glycoprotein IIb
  • Thrombospondin 1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Calcium