Physical and functional association of LFA-1 with DNAM-1 adhesion molecule.
Whereas ligation of the DNAM-1 adhesion molecule triggers cytotoxicity mediated by normal NK and T cells, this function was defective in NK cell clones from leukocyte adhesion deficiency syndrome. However, genetic reconstitution of cell surface expression of LFA-1 restored the ability of DNAM-1 to initiate anti-DNAM-1 mAb-induced cytotoxicity, indicating a functional relationship between DNAM-1 and LFA-1. Further studies demonstrated that LFA-1 physically associates with DNAM-1 in NK cells and anti-CD3 mAb stimulated T cells, for which serine phosphorylation of DNAM-1 plays a critical role. In addition, cross-linking of LFA-1 induces tyrosine phosphorylation of DNAM-1, for which the Fyn protein tyrosine kinase is responsible. These results indicate that DNAM-1 is involved in the LFA-1-mediated intracellular signals.
Pubmed ID: 10591186 RIS Download
Animals | Antibodies, Monoclonal | Antigens, CD3 | Antigens, Differentiation, T-Lymphocyte | COS Cells | Cell Adhesion | Cell Adhesion Molecules | Cercopithecus aethiops | Cytotoxicity, Immunologic | Genetic Complementation Test | Humans | Jurkat Cells | Killer Cells, Natural | Leukocyte-Adhesion Deficiency Syndrome | Lymphocyte Activation | Lymphocyte Function-Associated Antigen-1 | Mice | Phosphorylation | Phosphoserine | Protein Processing, Post-Translational | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-fyn | Signal Transduction | T-Lymphocytes | Tumor Cells, Cultured