The Tyrosine Phosphatase Shp2 in Development and Cancer

Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine

“…Shp2/Mek1DD double mutant mice are viable and develop no diarrhea or anal bleeding. For function, Shp2 is recruited to several tyrosine kinase receptors and other cell surface receptors (13). Compound Egfr wa-2 ; Shp2 +/− mutants exhibited intestinal defects, like desquamated epithelia and shortened villi (18), which are also observed in mild form in conditional Shp2 mutants.…”

“…The nonreceptor tyrosine phosphatase Shp2 mediates growth factor and cytokine signals and can regulate the activity of the Ras/Mek1/MAPK and other signaling pathways in development and disease (13,14). In mice, a null mutation of Shp2 interfered with the expansion of the trophoblast cell lineage and led to implantation deficits (15).…”

“…In mice, a null mutation of Shp2 interfered with the expansion of the trophoblast cell lineage and led to implantation deficits (15). Shp2 is also required for the development and maintenance of the nervous system, the kidney, and other organs (13,14,16,17); its role in the maintenance of the intestinal epithelium is not fully investigated. Heterozygous mutation of Shp2 in an Egfr mutant background resulted in the accumulation of desquamated intestinal epithelia (18).…”

Signaling to Cardiac Hypertrophy: Insights from Human and Mouse RASopathies

“…Moreover, for each tissue, or even cell type, there might be a threshold in the response to gain and loss in RAS signaling, dictated by the fact that oncogenes may convey both prosurvival and proapoptotic signals. This idea might explain why either decreasing or increasing SHP2 phosphatase activity has deleterious developmental consequences (109). Finally, cardiomyocytes might be less sensitive to a mutation for which the valves are more sensitive.…”

Grb2 controls phosphorylation of FGFR2 by inhibiting receptor kinase and Shp2 phosphatase activity

“…The C terminus of FGFR2 harbors numerous sites for the recruitment of downstream signaling effector proteins, thus perturbation of this region of FGFR2 can contribute to oncogenesis. Shp2 (also known as protein tyrosine phosphatase nonreceptor type 11 [PTPN11]) can be recruited by several RTKs either directly, or indirectly via auxiliary adaptor proteins (Freeman et al, 1992;Feng et al, 1993;Barford and Neel., 1998;Grossmann et al, 2010). Its phosphatase activity is thus important in regulation of intracellular signaling activity (HolgadoMadruga et al, 1996;Kouhara et al, 1997;Neel et al, 2010).…”