Shc

Summary

Gene Symbol: Shc
Description: SHC adaptor protein 1
Alias: SHC, SHCA, SHC-transforming protein 1, SH2 domain protein C1, SHC (Src homology 2 domain containing) transforming protein 1, SHC-transforming protein 3, SHC-transforming protein A
Species: human
Products:     Shc

Top Publications

  1. Sato K, Kimoto M, Kakumoto M, Horiuchi D, Iwasaki T, Tokmakov A, et al. Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells. Genes Cells. 2000;5:749-64 pubmed
    b>Shc is the adaptor protein that exists in three isoforms, P46, P52 and P66, and acts as a bridge between activated cell surface receptors and downstream signalling molecules which act in extracellular signal-regulated cell events such as ..
  2. Hellyer N, Kim M, Koland J. Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 co-receptor. J Biol Chem. 2001;276:42153-61 pubmed
    ..Recruitment of PI 3-kinase to ErbB3 was required for both activities, and it appeared that ErbB2 activation alone was not sufficient to activate PI 3-kinase signaling in these cells. ..
  3. Kisielow M, Kleiner S, Nagasawa M, Faisal A, Nagamine Y. Isoform-specific knockdown and expression of adaptor protein ShcA using small interfering RNA. Biochem J. 2002;363:1-5 pubmed
    ..We show how the adaptor protein ShcA can be suppressed and expressed in an isoform-specific manner in a human cell line...
  4. Franzeck F, Hof D, Spescha R, Hasun M, Akhmedov A, Steffel J, et al. Expression of the aging gene p66Shc is increased in peripheral blood monocytes of patients with acute coronary syndrome but not with stable coronary artery disease. Atherosclerosis. 2012;220:282-6 pubmed publisher
    ..p66Shc was associated with states of increased oxidative stress. Further work is needed to understand whether p66Shc may represent a possible pharmacological target or whether it represents an interesting novel biomarker. ..
  5. Lucs A, Muller W, Muthuswamy S. Shc is required for ErbB2-induced inhibition of apoptosis but is dispensable for cell proliferation and disruption of cell polarity. Oncogene. 2010;29:174-87 pubmed publisher
    ..Signals downstream of Tyr 1226/7 were also sufficient to confer paclitaxel resistance. The Tyr 1226/7 binds Shc, and the knockdown of Shc blocks the ability of ErbB2 to inhibit apoptosis and mediate paclitaxel resistance...
  6. Olayioye M, Graus Porta D, Beerli R, Rohrer J, Gay B, Hynes N. ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner. Mol Cell Biol. 1998;18:5042-51 pubmed
    ..In both cases, ErbB-1 coupled to the adaptor protein Shc, but only when activated by EGF was it able to interact with Grb2...
  7. Veeramani S, Igawa T, Yuan T, Lin F, Lee M, Lin J, et al. Expression of p66(Shc) protein correlates with proliferation of human prostate cancer cells. Oncogene. 2005;24:7203-12 pubmed
    p66(Shc), an isoform of Shc adaptor proteins, is shown to mediate various signals, including cellular stress. However, little is known about its involvement in carcinogenesis...
  8. Patrussi L, Savino M, Pellegrini M, Paccani S, Migliaccio E, Plyte S, et al. Cooperation and selectivity of the two Grb2 binding sites of p52Shc in T-cell antigen receptor signaling to Ras family GTPases and Myc-dependent survival. Oncogene. 2005;24:2218-28 pubmed
    b>Shc proteins participate in a variety of processes regulating cell proliferation, survival and apoptosis...
  9. Graus Porta D, Beerli R, Daly J, Hynes N. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 1997;16:1647-55 pubmed
    ..Finally, ErbB-1 activated by all EGF-related peptides (EGF, HB-EGF, BTC and NDF) couples to SHC, whereas only ErbB-1 activated by its own ligands associates with and phosphorylates Cbl...

More Information

Publications65

  1. Blagoev B, Kratchmarova I, Ong S, Nielsen M, Foster L, Mann M. A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling. Nat Biotechnol. 2003;21:315-8 pubmed
    ..protein Grb2 (GST-SH2 fusion protein) that specifically binds phosphorylated EGFR and Src homologous and collagen (Shc) protein. We identified 228 proteins, of which 28 were selectively enriched upon stimulation...
  2. Hinsby A, Olsen J, Mann M. Tyrosine phosphoproteomics of fibroblast growth factor signaling: a role for insulin receptor substrate-4. J Biol Chem. 2004;279:46438-47 pubmed
    ..Finally, we present evidence for a complex containing insulin receptor substrate-4 and ShcA in signaling by the fibroblast growth factor receptor.
  3. Pratt R, Kinch M. Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade. Oncogene. 2002;21:7690-9 pubmed
    ..Ligand-mediated activation allows EphA2 to form a molecular complex with the SHC and GRB2 adaptor proteins...
  4. Song R, Barnes C, Zhang Z, Bao Y, Kumar R, Santen R. The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor alpha to the plasma membrane. Proc Natl Acad Sci U S A. 2004;101:2076-81 pubmed
    ..17beta-estradiol (E2) rapidly induces the interaction of estrogen receptor alpha (ERalpha) with the adapter protein Shc, the translocation of ERalpha to the cell membrane, and the formation of dynamic membrane structures in MCF-7 ..
  5. Saucier C, Khoury H, Lai K, Peschard P, Dankort D, Naujokas M, et al. The Shc adaptor protein is critical for VEGF induction by Met/HGF and ErbB2 receptors and for early onset of tumor angiogenesis. Proc Natl Acad Sci U S A. 2004;101:2345-50 pubmed
    ..Moreover, the use of fibroblasts derived from ShcA-deficient mouse embryos, demonstrated that Shc was essential for the induction of VEGF by the Met/hepatocyte growth ..
  6. Batzer A, Rotin D, Urena J, Skolnik E, Schlessinger J. Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol. 1994;14:5192-201 pubmed
    ..Since Grb2 also binds Shc after EGF stimulation, we investigated whether Y-1173 is a binding site for the SH2 domain of Shc on the EGFR...
  7. Thelemann A, Petti F, Griffin G, Iwata K, Hunt T, Settinari T, et al. Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells. Mol Cell Proteomics. 2005;4:356-76 pubmed
    ..In addition to interactions with multiple signaling adaptors Grb2, SHC, SCK, and NSP2, EGF receptors in HN5 cells were shown to form direct or indirect physical interactions with ..
  8. Yukimasa S, Masaki T, Yoshida S, Uchida N, Watanabe S, Usuki H, et al. Enhanced expression of p46 Shc in the nucleus and p52 Shc in the cytoplasm of human gastric cancer. Int J Oncol. 2005;26:905-11 pubmed
    b>Shc protein is known to be related to cell proliferation and carcinogenesis. However, the involvement of Shc in gastric cancer remains unknown...
  9. Schulze W, Deng L, Mann M. Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol. 2005;1:2005.0008 pubmed
    ..We identified STAT5 as a direct binding partner to EGFR and ErbB4 and discovered new recognition motifs for Shc and STAT5...
  10. Northey J, Dong Z, Ngan E, Kaplan A, Hardy W, Pawson T, et al. Distinct phosphotyrosine-dependent functions of the ShcA adaptor protein are required for transforming growth factor ? (TGF?)-induced breast cancer cell migration, invasion, and metastasis. J Biol Chem. 2013;288:5210-22 pubmed publisher
    ..We previously demonstrated that ShcA is necessary for these synergistic interactions...
  11. Du W, Jiang Y, Zheng Z, Zhang Z, Chen N, Ma Z, et al. Feedback loop between p66(Shc) and Nrf2 promotes lung cancer progression. Cancer Lett. 2013;337:58-65 pubmed publisher
    p66(Shc), one of the SHC1 gene encoding proteins, promotes cell death and reports cell anchorage status, mediating anoikis in vitro and functioning as a metastasis suppressor in vivo...
  12. Skolnik E, Lee C, Batzer A, Vicentini L, Zhou M, Daly R, et al. The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. EMBO J. 1993;12:1929-36 pubmed
    ..is the major insulin receptor substrate IRS-1 and the second is the SH2 domain-containing oncogenic protein, Shc. The interactions between GRB2 and these two proteins require ligand activation of the insulin receptor and are ..
  13. Meakin S, MacDonald J, Gryz E, Kubu C, Verdi J. The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation. J Biol Chem. 1999;274:9861-70 pubmed
    ..of FRS-2 directly binds the Trk receptors at the same phosphotyrosine residue that binds the signaling adapter Shc, suggesting a model in which competitive binding between FRS-2 and Shc regulates differentiation versus ..
  14. Stephens R, Loeb D, Copeland T, Pawson T, Greene L, Kaplan D. Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses. Neuron. 1994;12:691-705 pubmed
    In response to NGF, the Trk receptor tyrosine kinase forms a complex with SHC, a protein that couples receptor tyrosine kinases to p21ras...
  15. van der Geer P, Wiley S, Lai V, Olivier J, Gish G, Stephens R, et al. A conserved amino-terminal Shc domain binds to phosphotyrosine motifs in activated receptors and phosphopeptides. Curr Biol. 1995;5:404-12 pubmed
    ..One such protein, Shc, is tyrosine phosphorylated in response to a large number of growth factors and cytokines...
  16. van der Geer P, Wiley S, Gish G, Lai V, Stephens R, White M, et al. Identification of residues that control specific binding of the Shc phosphotyrosine-binding domain to phosphotyrosine sites. Proc Natl Acad Sci U S A. 1996;93:963-8 pubmed
    The Shc adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules--an N-terminal Tyr(P) binding (PTB) domain and a C-terminal Src homology 2 (SH2) domain...
  17. Zhang W, Ji W, Yang L, Xu Y, Yang J, Zhuang Z. Epigenetic enhancement of p66Shc during cellular replicative or premature senescence. Toxicology. 2010;278:189-94 pubmed publisher
    ..Taken together, the epigenetic enhancement of p66Shc is associated with the specifically increased histone acetylation and methylation, which may contribute to cellular replicative senescence or premature senescence. ..
  18. Borkowska A, Sielicka Dudzin A, Herman Antosiewicz A, Halon M, Wozniak M, Antosiewicz J. P66Shc mediated ferritin degradation--a novel mechanism of ROS formation. Free Radic Biol Med. 2011;51:658-63 pubmed publisher
    ..DATS induced G2/M arrest in WT MEFs but had no effect in the p66Shc(-/-) cell line. Moreover, increases in LIP and ROS formation were significantly attenuated in p66Shc(-/-) MEFs treated with DATS...
  19. Shi Y, Cosentino F, Camici G, Akhmedov A, Vanhoutte P, Tanner F, et al. Oxidized low-density lipoprotein activates p66Shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase C-beta, and c-Jun N-terminal kinase kinase in human endothelial cells. Arterioscler Thromb Vasc Biol. 2011;31:2090-7 pubmed publisher
    Deletion of the mitochondrial gene p66(Shc) protects from endothelial dysfunction and atherosclerotic plaque formation in mice fed a high-fat diet...
  20. Migliaccio E, Mele S, Salcini A, Pelicci G, Lai K, Superti Furga G, et al. Opposite effects of the p52shc/p46shc and p66shc splicing isoforms on the EGF receptor-MAP kinase-fos signalling pathway. EMBO J. 1997;16:706-16 pubmed
    b>Shc proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to Ras...
  21. Oshikawa J, Kim S, Furuta E, Caliceti C, Chen G, McKinney R, et al. Novel role of p66Shc in ROS-dependent VEGF signaling and angiogenesis in endothelial cells. Am J Physiol Heart Circ Physiol. 2012;302:H724-32 pubmed publisher
    ..These studies uncover a novel role of p66Shc as a positive regulator for ROS-dependent VEGFR2 signaling linked to angiogenesis in ECs and suggest p66Shc as a potential therapeutic target for various angiogenesis-dependent diseases...
  22. Khanday F, Santhanam L, Kasuno K, Yamamori T, Naqvi A, Dericco J, et al. Sos-mediated activation of rac1 by p66shc. J Cell Biol. 2006;172:817-22 pubmed
    ..This relationship between p66shc, grb2, and sos1 provides a novel mechanism for the activation of rac1. ..
  23. Saucier C, Papavasiliou V, Palazzo A, Naujokas M, Kremer R, Park M. Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis. Oncogene. 2002;21:1800-11 pubmed
    ..Tpr-Met oncoprotein with the ability to bind individually to the p85 subunit of PI3'K, PLCgamma, or to the Grb2 or Shc adaptor proteins...
  24. Ravichandran K. Signaling via Shc family adapter proteins. Oncogene. 2001;20:6322-30 pubmed
    ..In addition to the ubiquitous ShcA, two other shc gene products, ShcB and ShcC, which are predominantly expressed in neuronal cells, have also been ..
  25. Foschi M, Franchi F, Han J, La Villa G, Sorokin A. Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its association with 14-3-3 protein in glomerular mesangial cells. J Biol Chem. 2001;276:26640-7 pubmed
    ..that ET-1 treatment of GMC results in serine phosphorylation of the 66-kDa isoform of the adapter protein Shc (p66(Shc))...
  26. Fournier E, Blaikie P, Rosnet O, Margolis B, Birnbaum D, Borg J. Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF receptor 3 signaling. Oncogene. 1999;18:507-14 pubmed
    The VEGFR3/FLT4 receptor, which is involved in vasculogenesis and angiogenesis, binds and phosphorylates SHC proteins on tyrosine residues...
  27. Chahdi A, Sorokin A. Endothelin-1 couples betaPix to p66Shc: role of betaPix in cell proliferation through FOXO3a phosphorylation and p27kip1 down-regulation independently of Akt. Mol Biol Cell. 2008;19:2609-19 pubmed publisher
    ..Our results identify p66Shc and FOXO3a as novel partners of beta(1)Pix and represent the first direct evidence of beta(1)Pix in cell proliferation via Erk/p66Shc-dependent and Akt-independent mechanisms. ..
  28. van der Geer P, Wiley S, Gish G, Pawson T. The Shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (Y239/240) that mediate protein-protein interactions. Curr Biol. 1996;6:1435-44 pubmed
    ..b>Shc is an adaptor protein that contains both PTB and SH2 domains and becomes phosphorylated on tyrosine in response to ..
  29. Borrello M, Pelicci G, Arighi E, De Filippis L, Greco A, Bongarzone I, et al. The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins. Oncogene. 1994;9:1661-8 pubmed
    ..We have shown that the SH2 domain of the adaptor protein Shc coimmunoprecipitates with all the Ret and Trk oncoproteins as well as with NGF-activated proto-Trk receptor...
  30. Veeramani S, Yuan T, Lin F, Lin M. Mitochondrial redox signaling by p66Shc is involved in regulating androgenic growth stimulation of human prostate cancer cells. Oncogene. 2008;27:5057-68 pubmed publisher
    ..These results collectively reveal a novel role for p66Shc-ROS pathway in androgen-induced prostate cancer cell proliferation and, thus, may play a role in early prostate carcinogenesis. ..
  31. Noda Y, Yamagishi S, Matsui T, Ueda S, Ueda S, Jinnouchi Y, et al. The p66shc gene expression in peripheral blood monocytes is increased in patients with coronary artery disease. Clin Cardiol. 2010;33:548-52 pubmed publisher
    The p66(shc) protein has been shown to control cellular responses to oxidative stress, being involved in atherosclerosis in animal models...
  32. Wagner K, Hemminki K, Grzybowska E, Klaes R, Butkiewicz D, Pamula J, et al. The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer. Carcinogenesis. 2004;25:2473-8 pubmed
    ..54, 95% CI 0.32-0.89, P = 0.01). A genotype combination analysis of the non-synonymous polymorphisms in the IRS1, IRS2 and SHC1 genes did not show any effect on breast cancer risk. ..
  33. Mooijaart S, van Heemst D, Schreuder J, van Gerwen S, Beekman M, Brandt B, et al. Variation in the SHC1 gene and longevity in humans. Exp Gerontol. 2004;39:263-8 pubmed
    Mice in which the p66(SHC) specific region of the SHC gene is deleted live 30% longer without apparent disease. These mice have lower levels of oxidative stress and apoptosis, both of which have been linked to old age survival in man...
  34. Ventura A, Luzi L, Pacini S, Baldari C, Pelicci P. The p66Shc longevity gene is silenced through epigenetic modifications of an alternative promoter. J Biol Chem. 2002;277:22370-6 pubmed
    The mammal Shc locus encodes three overlapping isoforms (46, 52, and 66 kDa) that differ in the length of their N-terminal regions...
  35. Gustafson T, He W, Craparo A, Schaub C, O Neill T. Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol Cell Biol. 1995;15:2500-8 pubmed
    The SHC proteins have been implicated in insulin receptor (IR) signaling. In this study, we used the sensitive two-hybrid assay of protein-protein interaction to demonstrate that SHC interacts directly with the IR...
  36. Levkowitz G, Waterman H, Ettenberg S, Katz M, Tsygankov A, Alroy I, et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol Cell. 1999;4:1029-40 pubmed
    ..Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways. ..
  37. Ong S, Guy G, Hadari Y, Laks S, Gotoh N, Schlessinger J, et al. FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors. Mol Cell Biol. 2000;20:979-89 pubmed
    ..dependent on phosphorylation of Y490, a canonical PTB domain binding site that also functions as a binding site for Shc (NPXpY)...
  38. Capitani N, Lucherini O, Sozzi E, Ferro M, Giommoni N, Finetti F, et al. Impaired expression of p66Shc, a novel regulator of B-cell survival, in chronic lymphocytic leukemia. Blood. 2010;115:3726-36 pubmed publisher
    ..Here, we show that the Shc family adapter p66Shc uncouples the B-cell receptor (BCR) from the Erk- and Akt-dependent survival pathways, ..
  39. Pelicci G, Lanfrancone L, McGlade J, Cavallo F, Forni G, Nicoletti I, et al. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. Cell. 1992;70:93-104 pubmed
    A new SH2-containing sequence, SHC, was isolated by screening cDNA libraries with SH2 representative DNA probes. The SHC cDNA is predicted to encode overlapping proteins of 46.8 and 51...
  40. Dikic I, Batzer A, Blaikie P, Obermeier A, Ullrich A, Schlessinger J, et al. Shc binding to nerve growth factor receptor is mediated by the phosphotyrosine interaction domain. J Biol Chem. 1995;270:15125-9 pubmed
    b>Shc is an adaptor protein that contains two phosphotyrosine-binding domains, a Src homology 2 (SH2) domain and the newly described phosphotyrosine interaction (PI) domain...
  41. Orsini F, Moroni M, Contursi C, Yano M, Pelicci P, Giorgio M, et al. Regulatory effects of the mitochondrial energetic status on mitochondrial p66Shc. Biol Chem. 2006;387:1405-10 pubmed
    p66(Shc) promotes apoptosis and controls the intracellular redox balance...
  42. Salcini A, McGlade J, Pelicci G, Nicoletti I, Pawson T, Pelicci P. Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins. Oncogene. 1994;9:2827-36 pubmed
    The mammalian SHC gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are phosphorylated on tyrosine by a variety of receptor and cytoplasmic tyrosine kinases...
  43. Pagnin E, Fadini G, De Toni R, Tiengo A, Calo L, Avogaro A. Diabetes induces p66shc gene expression in human peripheral blood mononuclear cells: relationship to oxidative stress. J Clin Endocrinol Metab. 2005;90:1130-6 pubmed
    ..The role of p66(shc) in oxidative stress-related response has been demonstrated by resistance to and reduction of oxidative stress and ..
  44. Ventura A, Maccarana M, Raker V, Pelicci P. A cryptic targeting signal induces isoform-specific localization of p46Shc to mitochondria. J Biol Chem. 2004;279:2299-306 pubmed
    The human Src homology and collagen (Shc) gene encodes three protein isoforms of 46, 52, and 66 kDa that belong to a family of molecular adapters involved in several signal transduction pathways...
  45. Gotoh N, Toyoda M, Shibuya M. Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activation. Mol Cell Biol. 1997;17:1824-31 pubmed
    Epidermal growth factor (EGF) induces tyrosine phosphorylation of the Shc adapter protein, which plays an important role in EGF-stimulated mitogenesis...
  46. Sakaguchi K, Okabayashi Y, Kido Y, Kimura S, Matsumura Y, Inushima K, et al. Shc phosphotyrosine-binding domain dominantly interacts with epidermal growth factor receptors and mediates Ras activation in intact cells. Mol Endocrinol. 1998;12:536-43 pubmed
    The adaptor protein Shc contains a phosphotyrosine binding (PTB) domain and a Src homology 2 (SH2) domain, both of which are known to interact with phosphorylated tyrosines...
  47. Sansone P, Storci G, Giovannini C, Pandolfi S, Pianetti S, Taffurelli M, et al. p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres. Stem Cells. 2007;25:807-15 pubmed
    ..We here report that the 66-kDa isoform of the SHC gene (p66Shc) is induced in a breast cancer cell line by the exposure to hypoxic environment and that it controls ..
  48. Grossman S, Lyle S, Resnick M, Sabo E, Lis R, Rosinha E, et al. p66 Shc tumor levels show a strong prognostic correlation with disease outcome in stage IIA colon cancer. Clin Cancer Res. 2007;13:5798-804 pubmed
    ..The abundance of the signal transduction proteins p66 Shc and tyrosine-phosphorylated (PY)-Shc in tumor cells is a prognostic indicator of disease outcome in breast cancer, ..
  49. Tong J, Taylor P, Peterman S, Prakash A, Moran M. Epidermal growth factor receptor phosphorylation sites Ser991 and Tyr998 are implicated in the regulation of receptor endocytosis and phosphorylations at Ser1039 and Thr1041. Mol Cell Proteomics. 2009;8:2131-44 pubmed publisher
    ..This reinforces the notion that EGFR function is manifest through spatially and temporally controlled protein-protein interactions and phosphorylations. ..
  50. Kumar A, Hoffman T, Dericco J, Naqvi A, Jain M, Irani K. Transcriptional repression of Kruppel like factor-2 by the adaptor protein p66shc. FASEB J. 2009;23:4344-52 pubmed publisher
    ..These findings illustrate a novel mechanism by which p66shc promotes cellular oxidative stress, through suppression of MEF2A expression and consequent repression of KLF2 transcription. ..
  51. Nemoto S, Combs C, French S, Ahn B, Fergusson M, Balaban R, et al. The mammalian longevity-associated gene product p66shc regulates mitochondrial metabolism. J Biol Chem. 2006;281:10555-60 pubmed
    Previous studies have determined that mice with a homozygous deletion in the adapter protein p66(shc) have an extended life span and that cells derived from these mice exhibit lower levels of reactive oxygen species...
  52. Park Y, Kim T, Lee S, Kim H, Kim S, Shong M, et al. p66Shc expression in proliferating thyroid cells is regulated by thyrotropin receptor signaling. Endocrinology. 2005;146:2473-80 pubmed
    ..Moreover, we suggest that TSH potentiates the regulatory effect of IGF-I on thyrocyte growth, at least in part, by increasing the expression of p66Shc. ..
  53. Obermeier A, Lammers R, Wiesmuller K, Jung G, Schlessinger J, Ullrich A. Identification of Trk binding sites for SHC and phosphatidylinositol 3'-kinase and formation of a multimeric signaling complex. J Biol Chem. 1993;268:22963-6 pubmed
    ..In vitro association of SHC and the p85 subunit of phosphatidylinositol 3'-kinase with the Trk tyrosine kinase was prevented only by ..
  54. O Bryan J, Songyang Z, Cantley L, Der C, Pawson T. A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is specifically expressed in the brain. Proc Natl Acad Sci U S A. 1996;93:2729-34 pubmed
    The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain and an N-terminal phosphotyrosine-binding (PTB) domain, and is itself ..
  55. Pacini S, Pellegrini M, Migliaccio E, Patrussi L, Ulivieri C, Ventura A, et al. p66SHC promotes apoptosis and antagonizes mitogenic signaling in T cells. Mol Cell Biol. 2004;24:1747-57 pubmed
    Of the three Shc isoforms, p66Shc is responsible for fine-tuning p52/p46Shc signaling to Ras and has been implicated in apoptotic responses to oxidative stress...
  56. Qian X, Riccio A, Zhang Y, Ginty D. Identification and characterization of novel substrates of Trk receptors in developing neurons. Neuron. 1998;21:1017-29 pubmed
    ..Together, these observations indicate that rAPS and SH2-B mediate Trk signaling in developing neurons. ..