The Shp-2 tyrosine phosphatase

Abstract

Shp-2 functions as a cytoplasmic protein tyrosine phosphatase in multiple fundamental cellular signaling pathways, to regulate basic mechanisms such as proliferation, differentiation, apoptosis, and motility. Notably, one genetic disorder in humans, Noonan Syndrome, has been linked to gain-of-function mutations in the Shp-2/PTPN11 gene, and this phosphatase also appears to be a cellular target of the Helicobacter pylori virulence factor CagA protein implicated in pathogenesis of gastric carcinoma. The requirement for Shp-2 activity in development has been demonstrated in vertebrate as well as in invertebrate models. While Shp-2 activity has been implicated in numerous signaling pathways, including the Ras/MAPK and JAK/STAT pathways, its physiological substrates remain elusive to investigators. This chapter provides a general background for Shp-2 signaling and discusses its contribution to a number of diverse biological functions in humans and other organisms.