Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line. The activation of Lyn tyrosine kinase and the mitogen-activated protein kinase pathway.
Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B cell activation. While it was originally believed that ICAM-1 played a purely adhesive role, recent evidence suggests that it can itself transduce biochemical signals. We demonstrate that cross-linking of ICAM-1 results in the up-regulation of class II major histocompatibility complex, and we investigate the biochemical mechanism for the signaling role of ICAM-1. We show that cross-linking of ICAM-1 on the B lymphoma line A20 induces an increase in tyrosine phosphorylation of several cellular proteins, including the Src family kinase p53/p56(lyn). In vitro kinase assays showed that Lyn kinase was activated within 1 min after ICAM-1 cross-linking. In addition, ICAM-1 cross-linking resulted in activation of Raf-1 and mitogen-activated protein kinases, as determined by gel mobility shift. Activation of these kinases may represent important components in the cascade of signals that link ICAM-1 to various ICAM-1-elicited cellular responses. These data confirm the important role of ICAM-1 as a signaling molecule in B cell activation.
Holland
J
J
Department of Microbiology and Immunology, McGill University, Neuroimmunology Unit, Montreal Neurological Institute, 3801 University, Montreal, Quebec, Canada H3A 2B4.
Owens
T
T
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D018799:Intercellular Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases