A unique interaction between alpha IIb and beta 3 in the head region is essential for outside-in signaling-related functions of alpha IIb beta 3 integrin

作者：Hauschner Hagit; Landau Meytal; Seligsohn Uri^*; Rosenberg Nurit

来源：Blood, 2010, 115(22): 4542-4550.

DOI：10.1182/blood-2009-10-251066

The main interface of the 2 subunits of platelet integrin alpha IIb beta 3 comprises the beta-propeller domain of alpha IIb and the beta A domain of beta 3. In the center of the beta-propeller, several aromatic residues interact by cation-pi and hydrophobic bonds with Arg261 of beta A. In this study, we substituted alpha IIb-Trp110 or beta 3-Arg261 by residues abundant in other alpha or beta subunits at corresponding locations and expressed them in baby hamster kidney cells along with normal beta 3 or alpha IIb, respectively. These mutant cells displayed normal surface expression and fibrinogen binding but grossly impaired outside-in signaling related functions: adhesion to immobilized fibrinogen, cell spreading, focal adhesion kinase phosphorylation, clot retraction, and reduced alpha IIb beta 3 stability in EDTA (ethylenediaminetetraacetic acid). Expression of mutants with substitutions of Arg261 in beta 3 by alanine or lysine with normal alpha v yielded normal surface expression of alpha v beta 3 and soluble fibrinogen binding as well as normal outside-in signaling related functions, contrasting findings for alpha IIb beta 3. Structural analysis of alpha IIb beta 3 and alpha v beta 3 revealed that alpha v beta 3 has several strong interactions between alpha v and beta 3 subunits that are missing in alpha IIb beta 3. Together, these findings indicate that the interaction between Trp110 of alpha IIb and Arg261 of beta 3 is critical for alpha IIb beta 3 integrity and outside-in signaling-related functions. (Blood. 2010; 115(22): 4542-4550)

• 出版日期2010-6-3