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

<正> Shp2,encoded by the PTPN11 gene in human,is aubiquitously expressed protein tyrosine phosphatase thatcontains two N-terminal Src homology 2(SH2)domains(N-SH2,C-SH2,respectively),a catalytic protein-tyrosinephosphatase(PTP)domain,and a C-terminal tail withtyrosyl phosphorylation sites and a prolyl-rich motif[1].The progress of our understanding of biological functionsof Shp2 has clearly shown that Shp2 plays an importantrole not only in biology of normal hematopoietic cells andother mammalian cells,but also in the development ofleukemia and other tumors.Most recently,PTPNll genehas been firmly established as the first proto-oncogene thatencodes a protein tyrosine phosphatase[1-3].In the hema-topoietic system,most if not all function of Shp2 is to actas a positive component that is essential for proliferationand/or survival of hematopoietic cells through regulationof signaling pathways involving Erk,Akt and STAT5[1-4].Over the past few years,a number of disease-associatedShp2 mutants have been identified in human leukemia andother malignancies[1,3,4].Recently,studies from ourlaboratories and others strongly suggest that dysregula-tion of wild-type Shp2 enzyme may be involved in the