She adaptor protein

Fig. 9.9 Model of the function of Grb2-mSos and the adaptor protein She in the Ras pathway. The figure shows a highly simplified version of the two known pathways of involvement of the Grb2-mSos complex in signal transduction via the Ras protein. Phosphotyrosine residues of an activated, auto-phosphorylated receptor R may serve as attachment points forthe PTB domains of the She adaptor protein (a) or forthe SH2 domain of the Grb2-mSos...

Signaling proteins that have been recruited to the activated receptor are often substrates for phosphorylation by the activated tyrosine kinase. Examples are the Stat proteins (see below), the She adaptor protein, and PI3 kinase. I1-2R/ activates PI3 kinase by inducing phosphorylation on tyrosine residues of the p80 regulatory subunit and recruiting PI3 kinase to the cell membrane. 

Ptasznik, A., Traynor-Kaplan, A.E. and Rokoch, G.M. (1995). G protein-coupled chemoattractant receptors regulate Lyn tyrosine kinase-She adaptor protein signaling complexes. J. Biol. Chem. 270, 19969-19 973. 

Classically, ERK is activated in the CNS via growth factors such as the neuronal growth factor (NGF) [31]. The binding of neurotrophins to Trk receptors induces the autophosphorylation of Trk, which subsequently allows the docking of the She adaptor protein (She). This triggers the phosphorylation of She and consequently the recruitment of the Grb2-SOS complex, which leads to the activation of the small G-protein Ras. Ras-GTP initiates the subsequent sequential phosphorylation of Rafl-kinase (a MAPKKK), MEKl/2 (a MAPKK), and finally ERKl/2 (MAPK) [32] (Fig. 1). A novel pathway leading to the activation of ERK 1/2 in neuronal cells, which is wholly Ca -dependent,... 

SHP binds to She (Sre Pomology and collagen) adaptor protein and to SHP-2 protein tyrosine phosphatase via SHIP S SH2 domain (Liu et al.,... 

In the other pathway, an additional adaptor protein, the She protein (see 8.5), is involved in the signal transduction. The She protein has a phosphotyrosine binding domain (PTB domain) and specifically binds via this domain to autophosphorylated receptors such as the PDGF receptor and the EGF receptor. The She protein is phos-phorylated itself in the process. The phosphotyrosine residues may also serve as attachment points for the SH2 domain of Grb2 protein, whereby the Grb2-Sos complex is attached to the membrane. 

This well characterized pathway of Ras signal transmission was the first to be discovered (see above) and involves adaptor proteins (Grb2, She) and GEFs (e.g. mSos). 

Heeneman S, Haendeler J, Saito Y, Ishida M, Berk BC. 2000. Angiotensin II induces transactivation of two different populations of the platelet-derived growth factor beta receptor. Key role for the p66 adaptor protein She. J Biol Chem 275 15926-15932. 

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