She protein

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. 

Pellegrini M, Pacini S, Baldari CT. p66SHC theapoptotic side of She proteins. Apoptosis,2005 10 13-18. 

Morte, C., Iborra, A., and Martinez, P. (1998). Phosphorylation of She proteins in human sperm in response to capacitation and progesterone treatment. Mol. Reprod. Dev. 50 113-120. 

A new secondary metabolite, 8-0-methylsclerotiorinamine (27), was isolated from a strain of Penicillium multicolor, and its structure was established using NMR spectroscopy and chemical evidence. The metabolite significantly inhibited the binding between the Grb2-SH2 domain and the phosphopeptide derived from the She protein and also blocked the protein-protein interactions of Grb2-Shc in cell-based experiments, with IC50 values of 5.3 and 50 pM, respectively [85]. 

Ras is known to be involved in the regulation of cellular proliferation and terminal differentiation [7,40]. In mammals, ras is activated by growth-factor-receptor tyrosine kinases and other tyrosine kinases. Some of these kinases phosphorylate the She protein and phosphorylated She plus autophosphorylated receptor proteins bind the SH2 domain... 

Aoto M, Sato K, Takeba S, Horiuchi Y, Iwasaki T, Tokmakov AA, Fukami Y. 1999. A 58-kDa She protein is present in Xenopus eggs and is phosphorylated on tyrosine residues upon egg activation. Biochem Biophys Res Gommun 258(2) 265-270. 

McGlade J, Cheng A, Pelicd G, Peliod PG, Pawson T. 1992. She proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases. Proc Natl Acad Sci US A89(19) 8869-8873. 

Gotoh N et al (1994b) Epidermal growth factor-receptor mutant lacking the autophosphorylation sites induces phosphorylation of She protein and Shc-Grb2/ASH association and retains mitogenic activity. Proc Natl Acad Sci USA 91 167-171... 

Ravichandran KS (2001) Signaling via She family adapter proteins. Oncogene 20 6322-6330... 

Among the substrates of Src are other nonreceptor PTKs (e.g., Fak, Syk, and Tec kinases), RTKs (e.g. EGF and PDGF receptors), phospholipase Cy, PI3-kinase, phosphatases (e.g., SHP-2 and PP2A), and adaptor (e.g., She and Cbl) as well as focal adhesion proteins (e.g., paxillin, pl30Cas andtensin). Src-mediated phosphorylation either modulates enzymatic activity of... 

Fig. 17. Cyclic voltammogram of the water-soluble Rieske fragment from the bci complex of Paracoccus denitrificans (ISFpd) at the nitric acid modified glassy carbon electrode. Protein concentration, 1 mg/ml in 50 mM NaCl, 10 mM MOPS, 5 mM EPPS, pH 7.3 T, 25°C scan rate, 10 mV/s. The cathodic (reducing branch, 7 < 0) and anodic (oxidizing branch, 7 > 0) peak potentisds Emd the resulting midpoint potential are indicated. SHE, standEU d hydrogen electrode.

She, Y. M. Haber, S. Siefers, D. L. Loboda, A. Chernushevich, I. Perreault, H. Ens, W. Standing, K. G. Determination of the complete amino acid sequence for the coat protein of brome mosaic virus by time-of-flight mass spectrometry Evidence for mutations associated with change of propagation host. J. Biol. Chem. 2001, 246, 20039-20047. 

Review articles fall somewhere between two extremes the he said this, she did that category and the what it all means category—summaries vs. syntheses. The reviews in this volume tend toward the latter type. Indeed, the whole volume can be regarded as one long synthesis describing the unfolded state of proteins as depicted in multiple, complementary perspectives. 

MAPK kinase (MAPKK). MAPK kinase itself is activated by phosphorylation by still another protein kinase, termed MAPK kinase kinase (MAPKKK). MAPK kinase kinase is activated upon interaction with a member of the Ras superfamily of small G proteins, which are bound to the plasma membrane (see Ch. 19). The exact mechanism of activation remains unknown, but it is believed that Ras and related proteins, in the activated GTP-bound form, can bind MAPK kinase kinase and thereby draw the kinase to the plasmalemma, where it is activated by as yet unknown factors, perhaps even an additional kinase, MAPK kinase kinase kinase (MAPKKKK). The mechanism governing the activation of Ras and related proteins by extracellular signals is quite complex and involves numerous Tinker proteins, for example She, Grb and Sos, that couple Ras to a variety of plasmalemma-associated growth factor-protein tyrosine kinase receptors (see Chs 20,24 and 27). 

Multiple interactions are also being demonstrated between the traditional second-messenger pathways and the MAPK cascades. Free (3y G protein subunits, generated upon activation of receptors coupled to the G family, lead to activation of the ERK pathway. The mechanism by which this occurs, which may involve an interaction between the subunits and Ras or Raf, is a subject of intensive research (see Ch. 19). In addition, increases in cellular Ca2+ concentrations lead to stimulation of the ERK pathway, apparently via phosphorylation by CaMKs of proteins, for example She and Grb, that link growth factor receptor tyrosine kinases to Ras. Activation of the... 

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