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Molecular and immunological basis of X‐linked lymphoproliferative disease
Author(s) -
Latour Sylvain,
Veillette André
Publication year - 2003
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2003.00023.x
Subject(s) - biology , tyrosine phosphorylation , immune system , proto oncogene tyrosine protein kinase src , receptor , gene , tyrosine kinase , sh2 domain , tyrosine , sh3 domain , microbiology and biotechnology , phosphorylation , receptor tyrosine kinase , genetics , biochemistry
Summary: 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.