PTPN11是致癌基因，编码蛋白（也称为SHP2）是一种蛋白酪氨酸磷酸酶，其从信号分子中除去磷酸基团。在无活性状态下，PTPN11保持抑制磷酸酶活性的构象。在生长因子或细胞因子刺激受体酪氨酸激酶（RTK）后，例如血小板衍生生长因子受体α（PDGFRA），PTPN11被募集到RTK上的磷酸化酪氨酸残基，从而导致构象变化和磷酸酶活性的激活。PTPN11调控多种信号传导，参与PI3K/Akt、STAT5和RAS/RAF/MEK/ERK信号通路的负调控。PNP11的胚系突变与在Noonan综合征和LEOPARD综合征相关；而PTPN11的体细胞突变在各种实体瘤和血液恶性肿瘤中发生改变，并且在青少年粒单核细胞白血病（JMML）中普遍发生。

PTPN11 (also known as SHP2) is a protein tyrosine phosphatase that removes phosphate groups from signaling molecules. In its resting inactive state, PTPN11 maintains a conformation that inhibits phosphatase activity. After growth factor or cytokine stimulation of a receptor tyrosine kinase (RTK), such as the platelet-derived growth factor receptor alpha (PDGFRA), PTPN11 is recruited to the phosphorylated tyrosine residue on the RTK leading to a conformational change and activation of phosphatase activity . PTPN11 regulates multiple signaling cascades and is involved in the negative regulation of the PI3K/AKT, STAT5 and RAS/RAF/MEK/ERK signaling pathways. Germline mutations in PTPN11 have been identified in Noonan syndrome and LEOPARD syndrome, while somatic PTPN11 mutations have been identified in several cancers and are prevalent in juvenile myelomonocytic leukemia (JMML). PTPN11 mutations typically occur as missense mutations that disrupt phosphatase activity or have dominant negative function, leading to the activation of signaling pathways that regulate growth. However, both gain-of-function and loss-of-function mutations can lead to pathway activation, as the open conformation of PTPN11 resulting from mutation matters more for its interaction with other proteins than does its catalytic activity. KRAS-mediated tumorigenesis has been shown to depend on functional PTPN11 protein .While PTPN11-specific therapies have not yet been developed, small molecule inhibitors targeting members of the RAF and PI3K signaling pathways have been found to be therapeutically effective in the context of PTPN11 loss.

GeneCards OncoKB My Cancer Genome