title: TCR-induced activation of LFA-1 involves signaling through Tiam1.
abstract: Adhesion is pivotal for most leukocyte functions, and the β(2) integrin family of adhesion molecules plays a central role. The integrins need activation to become functional, but the molecular events resulting in adhesion have remained incompletely understood. In human T cells, activation through the TCR results in specific phosphorylation of the T758 on the β(2) chain of LFA-1. We now show that this phosphorylation leads to downstream binding of 14-3-3 proteins, followed by engagement of the guanine nucleotide exchange factor protein Tiam1 and Rac1 activation. Downregulation of the signaling molecules inhibits LFA-1 activity. Activation by the chemokine stromal cell-derived factor-1α also results in T758 phosphorylation and integrin activation. Thus, TCR and chemokine activation converges on LFA-1 phosphorylation, followed by similar downstream events affecting adhesion.
authors.affiliation: Division of Biochemistry and Biotechnology, Department of Biosciences, University of Helsinki, 00014 Helsinki, Finland. Mikaela.gronholm@helsinki.fi
authors.forename: Mikaela
authors.initials: M
authors.lastname: Grönholm
authors.forename: Farhana
authors.initials: F
authors.lastname: Jahan
authors.forename: Silvia
authors.initials: S
authors.lastname: Marchesan
authors.forename: Ulla
authors.initials: U
authors.lastname: Karvonen
authors.forename: Maria
authors.initials: M
authors.lastname: Aatonen
authors.forename: Suneeta
authors.initials: S
authors.lastname: Narumanchi
authors.forename: Carl G
authors.initials: CG
authors.lastname: Gahmberg
mesh_terms: D048948:14-3-3 Proteins / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D015815:Cell Adhesion Molecules; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; C107953:RAC1 protein, human; D011948:Receptors, Antigen, T-Cell; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; D020830:rac1 GTP-Binding Protein