Identification of a new isoform of the murine Sh2d1a gene and its functional implications

查看全文 作　　者：WU [1]LongYan;LU [1]PeiWen;MA [1]WeiWei;CHU [1]CoCo;XU [1]HePing;QI [1]Hai

机构地区：[1]Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, School of Life Sciences,Tsinghua University

出　　处：《Science China(Life Sciences)》索引2014年第57卷第1期,共7页

基　　金：supported by funds from the Tsing-hua-Peking Center for Life Sciences;the National Natural Science Foundation of China(81072464) 摘　　要：Signaling lymphocytic activation molecule(SLAM)-associated protein(SAP)is a Src homology(SH)domain 2-containing intracellular adaptor protein that is predominantly expressed in the hematopoietic system by T lymphocytes and NK cells.SAP protein is encoded by the SH2D1A gene located on the X chromosome.Loss-of-function mutations in SAP cause the X-linked lymphoproliferative disease(XLP),a severe immunodeficiency characterized by heightened susceptibility to Epstein-Barr virus and impaired humoral immunity.Normal individuals express several functional and non-functional isoforms of SAP as a result of alternative splicing.In this study,we identify a cryptic exon in the murine Sh2d1a gene.At the mRNA level,the new isoform of SAP(SAP-2)that includes this new exon is widely expressed in lymphoid tissues by C57BL/6 and 129 strains of inbred mice.SAP-2 accounts for approximately 1%3%of total SAP transcripts,and it is dynamically regulated during lymphocyte activation.At the protein level,the SAP-2 isoform is a 144 amino-acid protein.Compared to the dominant 126 amino-acid SAP-1 isoform,the additional 18 amino acids are inserted into a structural region that is critical for phosphotyrosine binding.Our functional analysis in vitro indicates that SAP-2 is a non-functional isoform due to decreased protein stability.Thus,both human and mouse have multiple SAP splice isoforms that may or may not function.Modulation of relative proportions of these isoforms is potentially a mechanism whereby cells can regulate SAP-mediated biological activities. 关键词：近交系小鼠基因编码亚型 T淋巴细胞选择性剪接蛋白质水平鉴定相关蛋白

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Identification of a new isoform of the murine Sh2d1a gene and its functional implications

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