Shp2,a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia

Shp2 ，由 PTPN11 基因编码了为人，是包含二N终端 Src 相同的无所不在地表示的蛋白质酷氨酸磷酸酶 2 ( SH2 )领域( N-SH2 ， C-SH2 ，分别地)，一个催化蛋白质酷氨酸磷酸酶( PTP )领域，并且C终端与 tyrosyl 磷酸化地点和一个prolyl富有的主题跟踪。我们 Shp2 的生物函数的理解的进步清楚地证明了 Shp2 不仅在正常造血的房间和另外的哺乳动物的房间的生物学，而且在白血病和另外的肿瘤的开发起一个重要作用。最最近，当第一 proto-oncogenethat 编码蛋白质酷氨酸磷酸酶， PTPN11 基因坚定地被建立了。在造血的系统，最如果 Shp2 的并非所有功能是充当一个积极部件，那为通过表明包含英皇家空军之阶级最低之兵， Akt 和 STAT5 的小径的规定的造血的房间的增长或幸存是必要的。

Shp2, encoded by the PTPNll gene in human, is a ubiquitously expressed protein tyrosine phosphatase that contains two N-terminal Src homology 2 （SH2） domains （N-SH2, C-SH2, respectively）, a catalytic protein-tyrosine phosphatase （PTP） domain, and a C-terminal tail with tyrosyl phosphorylation sites and a prolyl-rich motif [1]. The progress of our understanding of biological functions of Shp2 has clearly shown that Shp2 plays an important role not only in biology of normal hematopoietic cells and other mammalian cells, but also in the development of leukemia and other tumors. Most recently, PTPNll gene has been firmly established as the first proto-oncogene that encodes a protein tyrosine phosphatase [1-3]. In the hematopoietic system, most if not all function of Shp2 is to act as a positive component that is essential for proliferation and/or survival of hematopoietic cells through regulation of signaling pathways involving Erk, Akt and STATS [ 1-4]. Over the past few years, a number of disease-associated Shp2 mutants have been identified in human leukemia and other malignancies [1, 3, 4]. Recently, studies from our laboratories and others strongly suggest that dysregulation of wild-type Shp2 enzyme may be involved in the pathogenesis of adult leukemia [4-7]. These findings not only provide new insights into the role of Shp2 in leukemogenesis and other tumors, but also suggest new therapeutic targets for anti-leukemia drugs.