The SAP family of adaptors in immune regulation.
SAP and EAT-2 define a new class of adaptor proteins composed almost exclusively of a Src homology 2 (SH2) domain. By way of their SH2 domain, SAP-like adaptors interact with tyrosine-based motifs in the cytoplasmic region of SLAM-related receptors, a family of immune cell-specific molecules involved in immunoregulation. Recent findings indicate that SAP is required for the functions of SLAM family receptors, as a consequence of its ability to promote recruitment of Src-related protein tyrosine kinase FynT and allow SLAM-related receptors to transduce tyrosine phosphorylation signals. SAP is mutated in X-linked lymphoproliferative (XLP) syndrome, a rare inherited human disease characterized by an deregulated immune response to Epstein-Barr virus infection. Several lines of evidence indicate that defects in the activities of SLAM-related receptors caused by SAP deficiency account for the immune dysfunctions associated with XLP.
Latour
Sylvain
S
Unité INSERM U429, Hôpital Necker Enfants-Malades, 149 rue de Sèvres, 75015 Paris, France. latour@necker.fr
Veillette
André
A
D048868:Adaptor Proteins, Signal Transducing / Q000145:classification / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007109:Immunity / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D015398:Signal Transduction; D013577:Syndrome
D048868:Adaptor Proteins, Signal Transducing