title: Role of SLAM-associated protein in the pathogenesis of autoimmune diseases and immunological disorders.
abstract: Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. SAP is expressed in T cells and natural killer (NK) cells and binds to the cytoplasmic domains of SLAM family receptors, resulting in the subsequent recruitment of Fyn. The SAP (SH2D1A) gene is located on the X chromosome and is responsible for X-linked lymphoproliferative disease, characterized by higher susceptibility to Epstein-Barr virus infection. The SAP-mediated signal is not only essential for the development of NKT cells, i.e. unconventional CD1d-restricted T cells with invariant Valpha14 T cell receptors, but also for the regulation of the function of NK cells and conventional T cells. The role of SAP-mediated signaling in the induction of autoimmune diseases has been analyzed using animal models such as lupus, hepatitis, and graft-versus-host disease and is considered important in their pathogenesis in humans. In this review we highlight the current findings on SAP-mediated signaling in hematopoietic cells and discuss its importance in autoimmune diseases and immunological disorders.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Aoba-ku, Sendai, Japan. hfurukawa@mail.tains.tohoku.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitazawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Komori
authors.forename: Masato
authors.initials: M
authors.lastname: Nose
authors.forename: Masao
authors.initials: M
authors.lastname: Ono
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1