Loading…

Phosphorylation of the LFA-1 Integrin β2-Chain on Thr-758 Leads to Adhesion, Rac-1/Cdc42 Activation, and Stimulation of CD69 Expression in Human T Cells

Phosphorylation of the leukocyte function-associated antigen-1 (LFA-1) integrin β2-chain on Thr-758 occurs after T cell receptor stimulation and leads to 14-3-3 recruitment to the integrin, actin cytoskeleton reorganization, and increased adhesion. Here, we have investigated the signaling effects of...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2007-01, Vol.282 (2), p.968-975
Main Authors: Nurmi, Susanna M., Autero, Matti, Raunio, Anna K., Gahmberg, Carl G., Fagerholm, Susanna C.
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Phosphorylation of the leukocyte function-associated antigen-1 (LFA-1) integrin β2-chain on Thr-758 occurs after T cell receptor stimulation and leads to 14-3-3 recruitment to the integrin, actin cytoskeleton reorganization, and increased adhesion. Here, we have investigated the signaling effects of β2 integrin Thr-758 phosphorylation. A penetratin-coupled phospho-Thr-758-β2 peptide (mimicking the part of the integrin β-chain surrounding Thr-758) stimulated adhesion of human T cells to the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Additionally, the peptide activated the small GTPases Rac-1 and Cdc42 in T cells. Constitutively active forms of Rac-1 and Cdc42, but not Rho, could compensate for the reduction of cell adhesion to ICAM-1 caused by the T758A mutation in the β2 integrin. Additionally, the active GTPases salvaged the cell-spreading defect of T758A integrin-transfected cells on coated ICAM-1. A dominant negative form of Cdc42, on the other hand, significantly reduced wild-type β2 integrin-mediated cell adhesion and spreading. In a T cell stimulation system, the pThr-758 penetratin peptide acted in a similar manner to coated ICAM-1 to increase T cell receptor-induced CD69 expression. These results show that Thr-758-phosphorylated LFA-1 is upstream of Rac-1/Cdc42, cell adhesion, and costimulatory activation of human T cells, thus identifying phosphorylation of Thr-758 in β2 as a proximal element in LFA-1 signaling.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M608524200