摘要
蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因位于染色体1p13．3-13．1，编码淋巴酪氨酸磷酸酶（LYP）。它通过与S忧酪氨酸激酶C端（Csk）相互作用，使已磷酸化的S忧家族Lck、Fyn和Zap-70激酶脱磷酸化，下调T细胞信号。另外，LYP还通过与Csk结合协同抑制T细胞信号，与转接分子——生长因子受体连接蛋白2（Grb2）相互作用，在T细胞信号中起负调节作用。研究发现，FTPN22基因C1858T位点错义突变，引起LYP蛋白620位密码子由精氨酸突变为色氨酸，与Csk亲和力明显降低，导致T细胞活性增强，可能诱发自身免疫性疾病。近来研究表明，该基因突变与1型糖尿病、Graves病和桥本甲状腺炎等多种自身免疫性内分泌疾病相关。
Protein tyrosine phosphatase, non-receptor 22 （PIPN22）gene locates in chromosome lp13.3- 13.1, which encodes a lymphoid protein tyrosine phosphatase （LYP）. It may be involved in preventing spontaneous T-cell activation by dephosphorylating and inactivating T-cell receptor-associated C-terminal Src tyrosine kinase （Csk）, down regulating T-cell signal. In addition, LYP inhibits T-cell activation by interacting with Csk. Probably it acts as a downregulator by interacting with the adaptor molecule growth factor receptor-bound protein 2（Grb2）. A missense mutant（C18587T, R620W）may decrease the binding affinity of LYP to CSK and result in higher T-cell activation and induce autoimmune disorders. Recently, a missense mutation in the PIPN22 gene has been shown to be associated with multiple autoimmune endocrine diseases including type 1 diabetes, Graves＇ disease and Hashimoto＇ s thyroiditis.
出处
《国际内分泌代谢杂志》
2007年第2期89-91,共3页
International Journal of Endocrinology and Metabolism
基金
重庆市卫生局科学基金资助项目（04-2-111）
