Structure, Function, and Pathogenesis of SHP2 in Developmental Disorders and Tumorigenesis
Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by the human PTPN11
gene, is a ubiquitously expressed protein tyrosine phosphatase (PTP) that consists of two tandem Src homology (SH2)
domains (N-SH2 and C-SH2), a PTP catalytic domain, and a C-terminal tail with tyrosyl phosphorylation sites. It plays
critical roles in numerous cellular processes through the regulation of various signaling pathways in PTP catalytic
activity-dependent and -independent manners. Dysfunction of SHP2 resulting from pathogenic mutations and aberrant
expression leads to the dysregulation of multiple signaling pathways, thus contributing to different human disorders.
Germline and somatic mutations in PTPN11 are involved in Noonan syndrome (NS), LEOPARD syndrome (LS), and
hematological malignancies, as well as several solid tumors. In this report, we provide an overview of the current
knowledge of the structure and function of SHP2, and further discuss the molecular and pathogenic mechanism of SHP2
in human diseases, with a special focus on tumorigenesis. Furthermore, we summarize that SHP2 might itself represent a
potential drug target for cancer prevention and treatment. Ongoing research and development of SHP2-specific inhibitors
would enhance this potential.
Keywords: Hematologic malignancies, LEOPARD syndrome, Noonan syndromes, PTPN11, SHP2, tumorigenesis.
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