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Shp2(SH2 domain-containing protein-tyrosine phosphatase-2)分子由PTPN11基因编码,是一个在体内广泛存在的非受体型蛋白酪氨酸磷酸酶,既可以通过磷酸酶的催化活性来正向调控下游信号转导通路,也可以作为磷酸酶非依赖性的接头蛋白发挥正向调控作用,在特定的条件下亦可发挥负向调控作用,从而广泛参与细胞的分化、迁移等生物学功能的调控及相关的信号转导过程。PTPN11突变被认为是青少年粒单细胞白血病(juvenile myelomonocytic leukemia,JMML)的高危因素,同时,因其在不同类型白血病中均存在着Shp2的异常活化和突变而被认为是白血病的原癌基因;在前列腺癌、乳腺癌、胰腺癌、胃癌和神经胶质瘤中,Shp2也被报道呈过度活化状态;在肺癌中Shp2作为癌基因通过调控多种机制促进肿瘤的发生、发展。但在肝癌发生过程中,Shp2却在特定环境的影响下发挥抑癌基因的作用。总之,作为重要的节点分子,Shp2在肿瘤发生、发展的过程中发挥着重要的调控作用,是潜在的治疗靶点。
Shp2 (SH2 domain-containing protein-tyrosine phosphatase-2) molecule encoded by the PTPN11 gene, is a non-receptor protein tyrosine phosphatase widespread in the body, both through the catalytic activity of phosphatase to regulate the downstream The signal transduction pathway can also play a positive regulatory role as a phosphatase-independent adapter protein and can also play a negative regulatory role under specific conditions, thereby widely participating in the regulation of biological functions such as cell differentiation and migration, and Related signal transduction processes. PTPN11 mutation is considered to be a risk factor for juvenile myelomonocytic leukemia (JMML). At the same time, PTPN11 mutation is considered as a protooncogene of leukemia due to the abnormal activation and mutation of Shp2 in different types of leukemia. Shp2 has also been reported to be overactive in prostate, breast, pancreas, stomach and gliomas. In lung cancer, Shp2 acts as an oncogene to promote tumorigenesis by regulating various mechanisms. However, in the process of liver cancer, Shp2 plays a role of tumor suppressor gene under the influence of specific environment. In conclusion, Shp2, as an important node molecule, plays an important regulatory role in tumorigenesis and development and is a potential therapeutic target.