title: Membrane-proximal signaling events in beta-2 integrin activation.
abstract: In the immune system, integrins have essential roles in leukocyte trafficking and function. These include immune cell attachment to endothelial and antigen-presenting cells, cytotoxicity, and extravasation into tissues. The integrin leukocyte function-associated antigen-1 (LFA-1), which is exclusively expressed on hematopoietic cells, has been intensely studied since this receptor is important for many functions of the immune system. LFA-1 is involved in a) the interaction between T-cells and antigen presenting cells, b) the adhesion of cells to post-capillary high endothelial venules or to activated endothelium at sites of inflammation (extravasation), c) the control of cell differentiation and proliferation, and d) the regulation of T-cell effector functions. Therefore, a precise understanding of the spatial and temporal control of LFA-1 interaction with its cellular counter-receptors, the intercellular adhesion molecules (ICAM) -1, -2 and -3, in the various contexts, is of high interest. LFA-1 mediated adhesion is induced by several extracellular stimuli in different cell types. In T-cells, LFA-1 becomes activated upon signaling from the T-cell receptor (TCR), and upon cytokine and chemokine sensing. Adhesion of monocytes to ICAM-1 is induced by lipopolysaccharide (LPS), a component of the bacterial cell wall. To investigate the regulation of LFA-1 adhesiveness, research has focused on the identification of interaction partners of the intracellular portions of the integrin alpha and beta subunits. This review will highlight recent developments on transmembrane and intracellular signaling proteins, which have been implicated in beta-2 integrin activation.
authors.affiliation: Life and Medical Sciences Institute (LIMES), Molecular Immune and Cell Biology Program Unit, Laboratory of Molecular Immunology, University of Bonn, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Kellersch
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
mesh_terms: D000818:Animals; D040881:CD11a Antigen / Q000502:physiology; D018821:CD18 Antigens / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D006801:Humans; D039641:Integrin beta Chains / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D040881:CD11a Antigen; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D039641:Integrin beta Chains; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1