title: Molecular and immunological basis of X-linked lymphoproliferative disease.
abstract: X-linked lymphoproliferative (XLP) disease is a human immune dysfunction characterized primarily by an inappropriate response to Epstein-Barr virus infection. In 1998, it was discovered that XLP is caused by inactivating mutations in the SAP/SH2D1A/DSHP gene. This gene codes for an immune cell-specific polypeptide termed SAP (SLAM-associated protein) that is composed almost exclusively of an Src homology 2 (SH2) domain. By way of its SH2 domain, SAP interacts with tyrosine-based motifs located in the cytoplasmic region of members of the SLAM (signaling lymphocyte activation molecule) family of receptors. Recent findings indicate that SAP is required for the function of SLAM-related receptors, as a consequence of its capacity to promote the recruitment and activation of the Src-related protein tyrosine kinase FynT, thereby allowing SLAM receptor-mediated protein tyrosine phosphorylation signals in immune cells. Functional and genetic analyses suggest that the phenotype associated with XLP is caused in large part by defects in the functions of SLAM-related receptors due to SAP deficiency.
authors.affiliation: Unité INSERM U429, Hôpital Necker Enfants-Malades, Paris, France. latour@necker.fr
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
authors.forename: André
authors.initials: A
authors.lastname: Veillette
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology*; D018448:Models, Immunological; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; 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