Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family.
Some CD2 family receptors stimulate NK cell-mediated cytotoxicity through a signaling pathway, which is dependent on the recruitment of an adapter protein called SLAM-associated protein (SAP). In this work we identify a novel leukocyte cell surface receptor of the CD2 family called CD2-like receptor activating cytotoxic cells (CRACC). CRACC is expressed on cytotoxic lymphocytes, activated B cells, and mature dendritic cells, and activates NK cell-mediated cytotoxicity. Remarkably, although CRACC displays cytoplasmic motifs similar to those recruiting SAP, CRACC-mediated cytotoxicity occurs in the absence of SAP and requires activation of extracellular signal-regulated kinases-1/2. Thus, CRACC is a unique CD2-like receptor which mediates NK cell activation through a SAP-independent extracellular signal-regulated kinase-mediated pathway.
Bouchon
A
A
Basel Institute for Immunology, Basel, Switzerland.
Cella
M
M
Grierson
H L
HL
Cohen
J I
JI
Colonna
M
M
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D018801:CD2 Antigens / Q000235:genetics*; D002352:Carrier Proteins / Q000502:physiology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011971:Receptors, Immunologic; D017386:Sequence Homology, Amino Acid; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018801:CD2 Antigens; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C114953:SH2D1A protein, human; C448987:SLAMF7 protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D020928:Mitogen-Activated Protein Kinases