The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway.
Shp2 is a ubiquitous tyrosine phosphatase containing Src Homology 2 domains which plays major biological functions in response to various growth factors, hormones or cytokines. This is essentially due to its particularity of promoting the activation of the Ras/Mitogen-activated protein kinase pathway. Recent progresses have been made in the understanding of the molecular mechanisms involved in this regulation. We review here, and discuss the physiological relevance, of the following molecular functions of Shp2 that have been proposed to couple the phosphatase to Ras activation: promoter of Grb2/Sos recruitment through direct binding to Grb2, binding partner and regulator of SHPS-1, negative regulator of Sprouty, negative regulator of RasGAP recruitment, and activator of Src through dephosphorylation of Src-regulatory proteins.
Dance
Marie
M
INSERM U563, Département Lipoprotéines et Médiateurs Lipidiques, Site Purpan, Toulouse, France.
Montagner
Alexandra
A
Salles
Jean-Pierre
JP
Yart
Armelle
A
Raynal
Patrick
P
D000818:Animals; D004789:Enzyme Activation; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism; D000099187:Major Vault Protein
D051380:GRB2 Adaptor Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D011971:Receptors, Immunologic; D020394:Vault Ribonucleoprotein Particles; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins; D019061:src-Family Kinases; D000099187:Major Vault Protein