Phosphorylation of the LFA-1 integrin beta 2-chain on Thr-758 leads to adhesion, Rac-1/Cdc42 activation and stimulation of CD69 expression in human T cells. Export

@article{citeulike:952661, abstract = {Phosphorylation of the LFA-1 integrin beta2-chain on Thr758 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 beta2-integrin Thr758-phosphorylation. A penetratin-coupled phospho-Thr758-beta2-peptide (mimicking the part of the integrin beta-chain surrounding Thr758) stimulated adhesion of human T cells to the LFA-1 ligand 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 beta2-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 wt-beta2-integrin mediated cell adhesion and spreading. In a T cell stimulation system, the pThr758-penetratin peptide acted in a similar manner to coated ICAM-1 to increase T cell receptor-induced CD69-expression. These results show that Thr758-phosphorylated LFA-1 is upstream of Rac-1/Cdc42, cell adhesion and costimulatory activation of human T cells, thus identifying phosphorylation of Thr758 in beta2 as a proximal element in LFA-1 signaling.}, address = {Department of Biological and Environmental Sciences, Division of Biochemistry, University of Helsinki, Helsinki 00014.}, author = {Nurmi, Susanna M M. and Autero, Matti and Raunio, Anna K K. and Gahmberg, Carl G G. and Fagerholm, Susanna C C.}, citeulike-article-id = {952661}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M608524200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/282/2/968}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17107954}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17107954}, day = {15}, doi = {10.1074/jbc.M608524200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {lfa-1}, month = {November}, posted-at = {2007-01-05 19:57:07}, priority = {3}, title = {Phosphorylation of the LFA-1 integrin beta 2-chain on Thr-758 leads to adhesion, Rac-1/Cdc42 activation and stimulation of CD69 expression in human T cells.}, url = {http://dx.doi.org/10.1074/jbc.M608524200}, year = {2006} }

TY - JOUR ID - citeulike:952661 L3 - citeulike-article-id:952661 N2 - Phosphorylation of the LFA-1 integrin beta2-chain on Thr758 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 beta2-integrin Thr758-phosphorylation. A penetratin-coupled phospho-Thr758-beta2-peptide (mimicking the part of the integrin beta-chain surrounding Thr758) stimulated adhesion of human T cells to the LFA-1 ligand 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 beta2-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 wt-beta2-integrin mediated cell adhesion and spreading. In a T cell stimulation system, the pThr758-penetratin peptide acted in a similar manner to coated ICAM-1 to increase T cell receptor-induced CD69-expression. These results show that Thr758-phosphorylated LFA-1 is upstream of Rac-1/Cdc42, cell adhesion and costimulatory activation of human T cells, thus identifying phosphorylation of Thr758 in beta2 as a proximal element in LFA-1 signaling. JF - J Biol Chem SN - 0021-9258 AD - Department of Biological and Environmental Sciences, Division of Biochemistry, University of Helsinki, Helsinki 00014. TI - Phosphorylation of the LFA-1 integrin beta 2-chain on Thr-758 leads to adhesion, Rac-1/Cdc42 activation and stimulation of CD69 expression in human T cells. KW - lfa-1 AU - Nurmi, Susanna M AU - Autero, Matti AU - Raunio, Anna K AU - Gahmberg, Carl G AU - Fagerholm, Susanna C PY - 2006/11/15/ UR - http://dx.doi.org/10.1074/jbc.M608524200 ER -