Ins and outs of LFA-1.

Leukocyte function-associated molecule 1 (LFA-1) is an integrin that plays a major role in the immune system. Recent findings demonstrate that LFA-1 has a two-way signaling function, mediating cell adhesion and stimulating intracellular processes at the same time. Here, Marijke Lub, Yvette van Kooyk and Carl Figdor discuss the 'inside-out' and 'outside-in' signaling properties of LFA-1, as a prototype leukocyte integrin, in normal and malignant T cells. They integrate data into a model that highlights the role of the cytoskeleton in the regulation of LFA-1.

[1]  C. Figdor,et al.  On the mode of action of LFA-1. , 1990, Immunology today.

[2]  A. Weiss,et al.  The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. , 1994, Annual review of immunology.

[3]  W. Newman,et al.  Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells. , 1994, Journal of immunology.

[4]  S. Wright,et al.  Integrin modulating factor-1: A lipid that alters the function of leukocyte integrins , 1992, Cell.

[5]  R. Pardi,et al.  Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travelers. , 1992, Immunology today.

[6]  J. Brugge,et al.  Adhesive signaling in platelets. , 1994, Current opinion in cell biology.

[7]  N. Hogg,et al.  Divalent cation regulation of the function of the leukocyte integrin LFA-1 , 1992, The Journal of cell biology.

[8]  F. Sánchez‐Madrid,et al.  Induction of tyrosine phosphorylation during ICAM-3 and LFA-1-mediated intercellular adhesion, and its regulation by the CD45 tyrosine phosphatase , 1994, The Journal of cell biology.

[9]  S. Wright,et al.  Aggregation of complement receptors on human neutrophils in the absence of ligand , 1987, The Journal of cell biology.

[10]  V. Moy,et al.  Signaling by lymphocyte function-associated antigen 1 (LFA-1) in B cells: enhanced antigen presentation after stimulation through LFA-1 , 1992, The Journal of experimental medicine.

[11]  T. O’Toole,et al.  Modulation of cell adhesion by changes in alpha L beta 2 (LFA-1, CD11a/CD18) cytoplasmic domain/cytoskeleton interaction , 1995, The Journal of experimental medicine.

[12]  Timothy A. Springer,et al.  The dynamic regulation of integrin adhesiveness , 1994, Current Biology.

[13]  F. Takei,et al.  Cell surface distribution of high-avidity LFA-1 detected by soluble ICAM-1-coated microspheres. , 1994, Journal of immunology.

[14]  John Calvin Reed,et al.  Protein tyrosine kinase p56-Lck regulates lymphocyte function-associated 1 adhesion molecule expression, granule exocytosis, and cytolytic effector function in a cloned T cell. , 1994 .

[15]  C. Figdor,et al.  Extracellular Ca2+ modulates leukocyte function-associated antigen-1 cell surface distribution on T lymphocytes and consequently affects cell adhesion , 1994, The Journal of cell biology.

[16]  T. Springer,et al.  The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 beta subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site , 1991, The Journal of experimental medicine.

[17]  Richard O. Hynes,et al.  Integrins: A family of cell surface receptors , 1987, Cell.

[18]  D. Cantrell.  G proteins in lymphocyte signalling. , 1994, Current opinion in immunology.

[19]  T. Hunter,et al.  Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase , 1994, Nature.

[20]  T. Tedder,et al.  Regulation of the tyrosine kinase-dependent adhesion pathway in human lymphocytes through CD45. , 1993, Journal of immunology.

[21]  C. Figdor,et al.  Lymphocyte function-associated antigen 1 dominates very late antigen 4 in binding of activated T cells to endothelium , 1993, The Journal of experimental medicine.

[22]  M. Arnaout,et al.  A novel divalent cation-binding site in the a domain of the β 2 integrin CR3 (CD11b/CD18) is essential for ligand binding , 1993, Cell.

[23]  T. Edgington,et al.  Microfilament reorganization is associated with functional activation of alpha M beta 2 on monocytic cells. , 1994, The Journal of biological chemistry.

[24]  B. Seed,et al.  T cell activation by clustered tyrosine kinases , 1993, Cell.

[25]  S. Dedhar.  Novel functions for calreticulin: interaction with integrins and modulation of gene expression? , 1994, Trends in biochemical sciences.

[26]  C. Figdor,et al.  Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes , 1989, Nature.

[27]  S. Laroche,et al.  Activation of human neutrophils induces an interaction between the integrin beta 2-subunit (CD18) and the actin binding protein alpha-actinin. , 1993, Journal of immunology.

[28]  A. M. Meijne,et al.  LFA-1 integrin redistribution during T-cell hybridoma invasion of hepatocyte cultures and manganese-induced adhesion to ICAM-1. , 1994, Journal of cell science.

[29]  M. Ticchioni,et al.  Engagement of the CD45 molecule induces homotypic adhesion of human thymocytes through a LFA-1/ICAM-3-dependent pathway. , 1994, Journal of immunology.

[30]  C. Figdor,et al.  Role of intracellular Ca2+ levels in the regulation of CD11a/CD18 mediated cell adhesion. , 1993, Cell adhesion and communication.

[31]  D. Ingber,et al.  Mechanotransduction across the cell surface and through the cytoskeleton , 1993 .

[32]  T. Springer,et al.  The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester , 1986, The Journal of experimental medicine.

[33]  N. Hogg,et al.  Macrophage cytoskeleton association with CR3 and CR4 regulates receptor mobility and phagocytosis of iC3b‐opsonized erythrocytes , 1992, Journal of leukocyte biology.

[34]  C. Figdor,et al.  Distinct binding of T lymphocytes to ICAM‐1, ‐2 or ‐3 upon activation of LFA‐1 , 1994, European journal of immunology.

[35]  B. Finlay,et al.  In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits. , 1991, Biochemistry.

[36]  Y. Shimizu,et al.  Differential activation-dependent regulation of integrin function in cultured human T-leukemic cell lines. , 1994, Blood.