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.
Shibuya
K
K
Department of Immunology, Institute of Basic Medical Sciences, Center for TARA, University of Tsukuba, Japan.
Lanier
L L
LL
Phillips
J H
JH
Ochs
H D
HD
Shimizu
K
K
Nakayama
E
E
Nakauchi
H
H
Shibuya
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex / Q000276:immunology; D019556:COS Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic; D005816:Genetic Complementation Test; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D000098862:T Lineage-Specific Activation Antigen 1
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D011518:Proto-Oncogene Proteins; D010768:Phosphoserine; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn