title: The SLAM and SAP gene families control innate and adaptive immune responses.
abstract: The nine SLAM-family genes, SLAMF1-9, a subfamily of the immunoglobulin superfamily, encode differentially expressed cell-surface receptors of hematopoietic cells. Engagement with their ligands, which are predominantly homotypic, leads to distinct signal transduction events, for instance those that occur in the T or NK cell immune synapse. Upon phosphorylation of one or more copies of a unique tyrosine-based signaling motif in their cytoplasmic tails, six of the SLAM receptors recruit the highly specific single SH2-domain adapters SLAM-associated protein (SAP), EAT-2A, and/or EAT-2B. These adapters in turn bind to the tyrosine kinase Fyn and/or other protein tyrosine kinases connecting the receptors to signal transduction networks. Individuals deficient in the SAP gene, SH2D1A, develop an immunodeficiency syndrome: X-linked lympho-proliferative disease. In addition to operating in the immune synapse, SLAM receptors initiate or partake in multiple effector functions of hematopoietic cells, for example, neutrophil and macrophage killing and platelet aggregation. Here we discuss the current understanding of the structure and function of these recently discovered receptors and adapter molecules in the regulation of adaptive and innate immune responses.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Calpe
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.forename: Xavier
authors.initials: X
authors.lastname: Romero
authors.forename: Scott B
authors.initials: SB
authors.lastname: Berger
authors.forename: Arpad
authors.initials: A
authors.lastname: Lanyi
authors.forename: Pablo
authors.initials: P
authors.lastname: Engel
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D000818:Animals; D006801:Humans; D007109:Immunity / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000503:physiopathology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000503:physiopathology; D008954:Models, Biological; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011971:Receptors, Immunologic; C114953:SH2D1A protein, human; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein