Protein Tyrosine Phosphatase SHP-2 as Drug Target

Protein tyrosine kinase (PTK) and tyrosine phosphatase (PTP) regulate various cellular processes. SHP-2, a ubiquitous non receptor type protein belongs to tyrosine phosphatase family. SHP-2 consists of two SH2 domain (N-SH2 and C-SH2), one C-terminal tail and a phosphatase domains. SHP2 is involved in regulating JAK-STAT and MAPK signaling pathways required for cell growth and differentiation. In the inactive form, SHP-2 is available in the closed conformation and gets activated after phosphorylation of tyrosine residues. SHP-2 protein is encoded with PTPN11 gene. Germline mutation in PTPN11 gene causes disruption in its closed conformation and causes over-expression of SHP-2 phosphatase activity. Deregulation of phosphatase activity leads to pathogenesis of cancer and diseases like Noonan and Leopard syndrome. Thus, SHP-2 inhibitors have been developed as a novel target for treating cancer and diseases caused due to abnormal cellular signaling. This review is a description of role of SHP-2 in cell physiology, diseases caused due to SHP-2 deregulation along with some SHP-2 inhibitors. Keywords: Leopard syndrome, noonan syndrome, protein tyrosine phosphatase, PTPN11, SHP-2, SHP-2 inhibitors.