Outside-in Integrin Signal Transduction

Autor: Lisa Nannizzi-Alaimo, David R. Phillips, Debbie A. Law
Rok vydání: 1996
Předmět:
Zdroj: Journal of Biological Chemistry. 271:10811-10815
ISSN: 0021-9258
DOI: 10.1074/jbc.271.18.10811
Popis: αIIbβ3-(GPIIb-IIIa) is the most abundant integrin expressed on platelets and plays a critical role in platelet aggregation and normal hemostasis. In response to platelet stimulation by agonists such as thrombin, αIIbβ3 becomes a receptor for the adhesive proteins fibrinogen, von Willebrand factor, vitronectin, and fibronectin. Binding of extracellular matrix ligands allows the integrin to transmit a signal to the inside of the cell, but the exact mechanisms whereby integrins transduce these signals remain unclear. In this paper we demonstrate that the β3 subunit of αIIbβ3 was phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation. However, tyrosine phosphorylation was not observed when platelets were stimulated by thrombin in the presence of an inhibitor of aggregation. Phosphotyrosine was only detected when platelets were solubilized under protein-denaturing conditions. A peptide corresponding to residues 740-762 of the β3 cytoplasmic domain was capable of binding the signaling proteins SHC and GRB2. GRB2 binding occurred only when both tyrosine residues (Tyr-747 and Tyr-759) were phosphorylated. SHC binding also occurred to a peptide monophosphorylated at Tyr-759. The data suggest that tyrosine phosphorylation of an integrin β subunit may be important in initiating outside-in signaling cascades by inducing association of signaling components directly with the integrin.
Databáze: OpenAIRE