title: Specific phosphorylations transmit signals from leukocyte β2 to β1 integrins and regulate adhesion.
abstract: The regulation of integrins expressed on leukocytes must be controlled precisely, and members of different integrin subfamilies have to act in concert to ensure the proper traffic of immune cells to sites of inflammation. The activation of β2 family integrins through the T cell receptor or by chemokines leads to the inactivation of very late antigen 4. The mechanism(s) of this cross-talk has not been known. We have now elucidated in detail how the signals are transmitted from leukocyte function-associated antigen 1 and show that, after its activation, the signaling involves specific phosphorylations of β2 integrin followed by interactions with cytoplasmic signaling proteins. This results in loss of β1 phosphorylation and a decrease in very late antigen 4 binding to its ligand vascular cell adhesion molecule 1. Our results show how a member of one integrin family regulates the activity of another integrin. This is important for the understanding of integrin-mediated processes.
authors.affiliation: Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Liisa M
authors.initials: LM
authors.lastname: Uotila
authors.affiliation: Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Farhana
authors.initials: F
authors.lastname: Jahan
authors.affiliation: Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Soto Hinojosa
authors.affiliation: Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Melandri
authors.affiliation: Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Grönholm
authors.affiliation: Division of Biochemistry and Biotechnology, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Carl G
authors.initials: CG
authors.lastname: Gahmberg
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D064448:Filamins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D016167:Integrin alphaXbeta2 / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D020014:K562 Cells; D007962:Leukocytes / Q000166:cytology*; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D018821:CD18 Antigens; D064448:Filamins; D039041:Integrin alpha4beta1; D016167:Integrin alphaXbeta2; D019012:Integrin beta1; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1
keywords: Adhesion; Integrin; LFA-1; Leukocyte; Phosphorylation; Signal Transduction; Transdominant Inhibition; VLA-4