Genomes and Genes
Gene Symbol: Shc1
Description: SHC adaptor protein 1
Alias: P66shc, SHC-transforming protein 1, SH2 domain protein C1, SHC (Src homology 2 domain containing) transforming protein 1, src homology 2 domain-containing-transforming protein C1
- Fernandes M, Saad M, Velloso L. Effects of age on elements of insulin-signaling pathway in central nervous system of rats. Endocrine. 2001;16:227-34 pubmed..Thus, elements involved in the insulin-signaling pathway are regulated at the expression and/or functional level in the CNS, and this regulation may play a role in insulin resistance in the brain. ..
- Puskas L, Nagy Z, Giricz Z, Onody A, Csonka C, Kitajka K, et al. Cholesterol diet-induced hyperlipidemia influences gene expression pattern of rat hearts: a DNA microarray study. FEBS Lett. 2004;562:99-104 pubmed..Although some of these genes have been suspected to be related to cardiovascular diseases, none of the genes has been previously shown to be involved in the mechanism of the cardiac effect of hyperlipidemia. ..
- Tang N, Lyu D, Liu T, Chen F, Jing S, Hao T, et al. Different Effects of p52SHC1 and p52SHC3 on the Cell Cycle of Neurons and Neural Stem Cells. J Cell Physiol. 2016;231:172-80 pubmed publisherSHC3 is exclusively expressed in postmitotic neurons, while SHC1 is found in neural stem cells and neural precursor cells but absent in mature neurons...
- Howard P, Chia M, Del Rizzo S, Liu F, Pawson T. Redirecting tyrosine kinase signaling to an apoptotic caspase pathway through chimeric adaptor proteins. Proc Natl Acad Sci U S A. 2003;100:11267-72 pubmed..These hybrid adaptors can be used to selectively kill oncogenic cells in which RTK activity is deregulated. ..
- McGlade J, Cheng A, Pelicci G, Pelicci P, Pawson T. Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1992;89:8869-73 pubmed
- Vindis C, Cerretti D, Daniel T, Huynh Do U. EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. J Cell Biol. 2003;162:661-71 pubmed..Together these findings highlight a new aspect of EphB1 signaling, whereby the concerted action of c-Src and p52Shc activates MAPK/ERK and regulates events involved in cell motility. ..
- Ott V, Tamir I, Niki M, Pandolfi P, Cambier J. Downstream of kinase, p62(dok), is a mediator of Fc gamma IIB inhibition of Fc epsilon RI signaling. J Immunol. 2002;168:4430-9 pubmed..Taken together, these data suggest a role for p62(dok) as a mediator of Fc gamma RIIB inhibition of Fc epsilon RI signal transduction in mast cells. ..
- Graiani G, Lagrasta C, Migliaccio E, Spillmann F, Meloni M, Madeddu P, et al. Genetic deletion of the p66Shc adaptor protein protects from angiotensin II-induced myocardial damage. Hypertension. 2005;46:433-40 pubmed..In cultured vascular smooth muscle cells, this downstream mechanism comprises the p66Shc adaptor protein, previously recognized to play a role in vascular cell senescence and death...
- MacLaren R, Cui W, Simard S, Cianflone K. Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue. J Lipid Res. 2008;49:308-23 pubmed..05). Together, microarray and real-time PCR data demonstrate that insulin resistance rather than obesity is associated with altered gene expression of insulin signaling genes, especially in OM adipose tissue. ..
- Kasus Jacobi A, Perdereau D, Auzan C, Clauser E, Van Obberghen E, Mauvais Jarvis F, et al. Identification of the rat adapter Grb14 as an inhibitor of insulin actions. J Biol Chem. 1998;273:26026-35 pubmed..These findings suggest that rGrb14 could be a new downstream signaling component of the insulin-mediated pathways. ..
- Arany I, Carter A, Hall S, Fulop T, Dixit M. Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66shc-dependent antioxidant responses. Apoptosis. 2017;22:220-228 pubmed publisher..the anti-oxidant/anti-apoptotic effect of Coenzyme Q10 on nicotine-induced oxidative stress and its impact on p66shc in cultured rat renal proximal tubule cells (NRK52E)...
- Smith W, Norton D, Gorospe M, Jiang H, Nemoto S, Holbrook N, et al. Phosphorylation of p66Shc and forkhead proteins mediates Abeta toxicity. J Cell Biol. 2005;169:331-9 pubmed..Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in Abeta toxicity...
- Soltoff S. Related adhesion focal tyrosine kinase and the epidermal growth factor receptor mediate the stimulation of mitogen-activated protein kinase by the G-protein-coupled P2Y2 receptor. Phorbol ester or [Ca2+]i elevation can substitute for receptor activat. J Biol Chem. 1998;273:23110-7 pubmed..Although P2Y2 and EGF receptors may both activate a similar multiprotein signaling cascade immediately upstream of MAP kinase, the P2Y2 receptor appears to uniquely utilize [Ca2+]i, PKC, and, subsequently, RAFTK. ..
- Wang J, Tao J, Chen D, Cai J, Irani K, Wang Q, et al. MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014;34:99-109 pubmed publisher..miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.
- Craparo A, O Neill T, Gustafson T. Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem. 1995;270:15639-43 pubmed..We conclude that the interactions of SHC and IRS-1 with the IGFIR are similar to those which we have previously defined with the insulin receptor. ..
- Bianchi G, Di Giulio C, Rapino C, Rapino M, Antonucci A, Cataldi A. p53 and p66 proteins compete for hypoxia-inducible factor 1 alpha stabilization in young and old rat hearts exposed to intermittent hypoxia. Gerontology. 2006;52:17-23 pubmed
- Tian X, Hu Y, Li M, Xia K, Yin J, Chen J, et al. Carnosic acid attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway. Can J Physiol Pharmacol. 2016;94:416-25 pubmed publisher..We previously demonstrated that SIRT1/p66Shc pathway activation attenuates hepatocyte apoptosis in liver ischemia/reperfusion...
- Tacconelli A, Farina A, Cappabianca L, Desantis G, Tessitore A, Vetuschi A, et al. TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell. 2004;6:347-60 pubmed
- Jiang X, Edstrom E, Altun M, Ulfhake B. Differential regulation of Shc adaptor proteins in skeletal muscle, spinal cord and forebrain of aged rats with sensorimotor impairment. Aging Cell. 2003;2:47-57 pubmed..The coup-regulation of p66(ShcA) and p75(NTR) is interesting since both molecules have been associated with apoptosis. ..
- 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..These results demonstrate that p66(shc) regulates mitochondrial oxidative capacity and suggest that p66(shc) may extend life span by repartitioning metabolic energy conversion away from oxidative and toward glycolytic pathways. ..
- Lee S, Kim H, Song Y, Joo H, Lee J, Lee K, et al. Alteration of p66shc is associated with endothelial dysfunction in the abdominal aortic coarctation of rats. FEBS Lett. 2008;582:2561-6 pubmed publisherTo examine the role of p66shc in endothelial dysfunction, we investigated the endothelium-dependent relaxation, protein expression and superoxide production in abdominal aortic coarctation rats...
- Kwon H, Lee J, Jeong K, Jang D, Pak Y. Fatty acylated caveolin-2 is a substrate of insulin receptor tyrosine kinase for insulin receptor substrate-1-directed signaling activation. Biochim Biophys Acta. 2015;1853:1022-34 pubmed publisher..In conclusion, fatty acylated cav-2 is a new substrate of IR tyrosine kinase, and the fatty acylation and phosphorylation of cav-2 present novel mechanisms by which insulin signaling is activated. ..
- Wada T, Naito M, Kenmochi H, Tsuneki H, Sasaoka T. Chronic nicotine exposure enhances insulin-induced mitogenic signaling via up-regulation of alpha7 nicotinic receptors in isolated rat aortic smooth muscle cells. Endocrinology. 2007;148:790-9 pubmed
- Gentile A, Trusolino L, Comoglio P. The Met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev. 2008;27:85-94 pubmed publisher..Several approaches have been recently developed to interfere with the tumorigenic and metastatic processes triggered by Met. ..
- Kimura T, Kihara H, Bhattacharyya S, Sakamoto H, Appella E, Siraganian R. Downstream signaling molecules bind to different phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) peptides of the high affinity IgE receptor. J Biol Chem. 1996;271:27962-8 pubmed..Tyrosine phosphorylation of the ITAM of the gamma subunit recruits and activates Syk, whereas the beta subunit may be important for the Ras signaling pathway. ..
- Yoshida S, Masaki T, Feng H, Yuji J, Miyauchi Y, Funaki T, et al. Enhanced expression of adaptor molecule p46 Shc in nuclei of hepatocellular carcinoma cells: study of LEC rats. Int J Oncol. 2004;25:1089-96 pubmed
- Sone K, Mori M, Mori N. Selective upregulation of p66-Shc gene expression in the liver and brain of aged rats. Arch Gerontol Geriatr. 2012;55:744-8 pubmed publisher..These results indicate that p66-Shc is not only related to animal longevity but also affected during aging, and thus the repression of p66-Shc could become a potential target for an anti-aging strategy. ..
- Shan W, Gao L, Zeng W, Hu Y, Wang G, Li M, et al. Activation of the SIRT1/p66shc antiapoptosis pathway via carnosic acid-induced inhibition of miR-34a protects rats against nonalcoholic fatty liver disease. Cell Death Dis. 2015;6:e1833 pubmed publisher..Importantly, the decrease in miR-34a expression was closely associated with the activation of the SIRT1/p66shc pathway, which attenuates hepatocyte apoptosis in liver ischemia/reperfusion injury...
- Zheng Y, Zhang C, Croucher D, Soliman M, St Denis N, Pasculescu A, et al. Temporal regulation of EGF signalling networks by the scaffold protein Shc1. Nature. 2013;499:166-71 pubmed publisher..Activated receptor tyrosine kinases, for example, engage scaffolds such as Shc1 that contain phosphotyrosine (pTyr)-binding (PTB) domains...
- Sasaoka T, Rose D, Jhun B, Saltiel A, Draznin B, Olefsky J. Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-1, and epidermal growth factor. J Biol Chem. 1994;269:13689-94 pubmed..The functional locus of Shc is either upstream of p21ras or lies on a distinct branch of the pathway leading to cell cycle progression. ..
- Ugi S, Imamura T, Ricketts W, Olefsky J. Protein phosphatase 2A forms a molecular complex with Shc and regulates Shc tyrosine phosphorylation and downstream mitogenic signaling. Mol Cell Biol. 2002;22:2375-87 pubmed
- Jensen M, Hansen B, De Meyts P, Schäffer L, Ursø B. Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses. J Biol Chem. 2007;282:35179-86 pubmed..We show for the first time that it is possible to design insulin receptor ligand mimetics with metabolic equipotency but low mitogenicity. ..
- Abou Rjaily G, Lee S, May D, Al Share Q, Deangelis A, Ruch R, et al. CEACAM1 modulates epidermal growth factor receptor--mediated cell proliferation. J Clin Invest. 2004;114:944-52 pubmed..Thus, L-SACC1 mice provide a model for the mechanistic link between increased cell proliferation in states of impaired metabolism and visceral obesity. ..
- Sayeski P, Ali M. The critical role of c-Src and the Shc/Grb2/ERK2 signaling pathway in angiotensin II-dependent VSMC proliferation. Exp Cell Res. 2003;287:339-49 pubmed..Thus, the data suggest that c-Src and the Shc/Grb2/ERK2 signaling pathway play a critical role in angiotensin II-mediated VSMC proliferation. ..
- Dalle S, Imamura T, Rose D, Worrall D, Ugi S, Hupfeld C, et al. Insulin induces heterologous desensitization of G-protein-coupled receptor and insulin-like growth factor I signaling by downregulating beta-arrestin-1. Mol Cell Biol. 2002;22:6272-85 pubmed
- Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7:505-16 pubmed..Because network fragility is an inevitable trade-off of robustness, systems-level understanding is expected to generate therapeutic opportunities to intercept aberrant network activation. ..
- Natalicchio A, Laviola L, De Tullio C, Renna L, Montrone C, Perrini S, et al. Role of the p66Shc isoform in insulin-like growth factor I receptor signaling through MEK/Erk and regulation of actin cytoskeleton in rat myoblasts. J Biol Chem. 2004;279:43900-9 pubmed..L6/Shcas myoblasts showed marked reduction of the p66Shc protein isoform and no change in p52Shc or p46Shc proteins compared with control myoblasts transfected with the ..
- Guo J, Gertsberg Z, Ozgen N, Steinberg S. p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes. Circ Res. 2009;104:660-9 pubmed publisherb>p66Shc is an adapter protein that is induced by hypertrophic stimuli and has been implicated as a major regulator of reactive oxygen species (ROS) production and cardiovascular oxidative stress responses...
- Gupta V, You Y, Gupta V, Klistorner A, Graham S. TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders. Int J Mol Sci. 2013;14:10122-42 pubmed publisher..In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches. ..
- 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 SAIN domain appears to represent a novel motif which is able to interact with autophosphorylated receptors such as the IR. ..
- Blaikie P, Immanuel D, Wu J, Li N, Yajnik V, Margolis B. A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors. J Biol Chem. 1994;269:32031-4 pubmed..Our data define a novel domain in Shc that has the potential to interact with growth factor receptors and other tyrosine-phosphorylated proteins. ..
- Calvert V, Collantes R, Elariny H, Afendy A, Baranova A, Mendoza M, et al. A systems biology approach to the pathogenesis of obesity-related nonalcoholic fatty liver disease using reverse phase protein microarrays for multiplexed cell signaling analysis. Hepatology. 2007;46:166-72 pubmed..These findings provide evidence for the role of omental fat in the pathogenesis, and potentially, the progression of NAFLD. ..
- Poy M, Ruch R, Fernstrom M, Okabayashi Y, Najjar S. Shc and CEACAM1 interact to regulate the mitogenic action of insulin. J Biol Chem. 2002;277:1076-84 pubmed..Thus, binding to Shc appears to constitute a major mechanism for the down-regulatory effect of CEACAM1 on cell proliferation. ..
- Abramson J, Pecht I. Clustering the mast cell function-associated antigen (MAFA) leads to tyrosine phosphorylation of p62Dok and SHIP and affects RBL-2H3 cell cycle. Immunol Lett. 2002;82:23-8 pubmed..We therefore suggest that MAFA has also a role in regulating RBL-2H3 cell proliferation rate by inhibiting RasGTP formation in the Ras signaling pathway. ..
- Obreztchikova M, Elouardighi H, Ho M, Wilson B, Gertsberg Z, Steinberg S. Distinct signaling functions for Shc isoforms in the heart. J Biol Chem. 2006;281:20197-204 pubmed..We show that thrombin increases p46Shc/p52Shc phosphorylation at Tyr(239)/Tyr(240) and Tyr(317) (and p66Shc-Ser(36) phosphorylation) via a pertussis toxin-insensitive epidermal growth factor receptor (EGFR) transactivation ..
- Lai K, Pawson T. The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo. Genes Dev. 2000;14:1132-45 pubmed..ShcA may therefore orchestrate complex interactions within the vascular compartment by rendering cells permissive to respond to soluble and adhesive external cues. ..
- Park R, Kim D, Kim M, So H, Chung H, Kwon K, et al. Association of Shc, Cbl, Grb2, and Sos following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in primary rat hepatocytes. Biochem Biophys Res Commun. 1998;253:577-81 pubmed..Furthermore, tyrosine phosphorylation of Cbl may not be critical for interaction of the protein with Grb2 and Shc in the TCDD signaling pathway in primary rat hepatocytes. ..
- Sasaoka T, Kikuchi K, Wada T, Sato A, Hori H, Murakami S, et al. Dual role of SRC homology domain 2-containing inositol phosphatase 2 in the regulation of platelet-derived growth factor and insulin-like growth factor I signaling in rat vascular smooth muscle cells. Endocrinology. 2003;144:4204-14 pubmed
- Yamamori T, White A, Mattagajasingh I, Khanday F, Haile A, Qi B, et al. P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction. J Mol Cell Cardiol. 2005;39:992-5 pubmedThe p66shc adaptor protein mediates age-associated oxidative stress. We examined the role of p66shc in endothelial nitric oxide synthase (eNOS) signaling. Overexpression of p66shc inhibited eNOS-dependent NO production...
- Bashir M, Parray A, Baba R, Bhat H, Bhat S, Mushtaq U, et al. ?-Amyloid-evoked apoptotic cell death is mediated through MKK6-p66shc pathway. Neuromolecular Med. 2014;16:137-49 pubmed publisherWe have previously shown the involvement of p66shc in mediating apoptosis. Here, we demonstrate the novel mechanism of ?-Amyloid-induced toxicity in the mammalian cells...
- Reed D, Carter A, Dixit M, Arany I. p66shc-mediated toxicity of high-dose ?-tocopherol in renal proximal tubule cells. J Physiol Biochem. 2017;73:267-273 pubmed publisher..Since the pro-oxidant p66shc is a major mediator of oxidant injury in various models of renal toxicants, we tested the hypothesis that hTOC ..
- Miller B, Palygin O, Rufanova V, Chong A, Lazar J, Jacob H, et al. p66Shc regulates renal vascular tone in hypertension-induced nephropathy. J Clin Invest. 2016;126:2533-46 pubmed publisher..Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated ..
- Geetha T, Jiang J, Wooten M. Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling. Mol Cell. 2005;20:301-12 pubmed..These findings reveal that polyubiquitination serves as a common platform for the control of receptor internalization and signaling. ..
- Hinsby A, Lundfald L, Ditlevsen D, Korshunova I, Juhl L, Meakin S, et al. ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation. J Neurochem. 2004;91:694-703 pubmed
- Yuji J, Masaki T, Yoshida S, Kita Y, Feng H, Uchida N, et al. Identification of p46 Shc expressed in the nuclei of hepatocytes with high proliferating activity: Study of regenerating rat liver. Int J Mol Med. 2004;13:721-8 pubmed..Therefore, it is suggested that p46 Shc expressed in hepatocellular nuclei may be a useful marker for detecting hepatocytes with high proliferative activity. ..
- Birchmeier C, Birchmeier W, Gherardi E, Vande Woude G. Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 2003;4:915-25 pubmed
- Carloni V, Mazzocca A, Ravichandran K. Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc in liver tumor cells. Oncogene. 2004;23:1566-74 pubmed..These findings define a novel mechanism of ERK/MAPKinase activation and tumor cell proliferation. ..
- Heinrich C, Keller C, Boulay A, Vecchi M, Bianchi M, Sack R, et al. Copine-III interacts with ErbB2 and promotes tumor cell migration. Oncogene. 2010;29:1598-610 pubmed publisher..Moreover, in an in situ tissue microarray analysis, we detected differential protein expression of Copine-III in normal versus breast, prostate and ovarian tumors, suggesting a more general role for Copine-III in carcinogenesis. ..
- Malhotra A, Vashistha H, Yadav V, Dube M, Kalra S, Abdellatif M, et al. Inhibition of p66ShcA redox activity in cardiac muscle cells attenuates hyperglycemia-induced oxidative stress and apoptosis. Am J Physiol Heart Circ Physiol. 2009;296:H380-8 pubmed publisher..We conclude that p66ShcA is a molecular switch whose redox function is turned on by phospho-Ser36 and turned off by interventions that prevent this modification. ..
- Balbis A, Parmar A, Wang Y, Baquiran G, Posner B. Compartmentalization of signaling-competent epidermal growth factor receptors in endosomes. Endocrinology. 2007;148:2944-54 pubmed..These observations suggest that a distinctive pool of endocytic EGFR, potentially competent for signaling, is actively trafficking through intracellular compartments with the characteristic of lipid rafts. ..
- Youngren J. Regulation of insulin receptor function. Cell Mol Life Sci. 2007;64:873-91 pubmed..The impact of these processes on the conformational changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human disease, is reviewed in this article. ..
- Piiper A, Dikic I, Lutz M, Leser J, Kronenberger B, Elez R, et al. Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells. J Biol Chem. 2002;277:43623-30 pubmed
- Camici G, Schiavoni M, Francia P, Bachschmid M, Martin Padura I, Hersberger M, et al. Genetic deletion of p66(Shc) adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress. Proc Natl Acad Sci U S A. 2007;104:5217-22 pubmed..These data suggest that p66(Shc) adaptor protein is part of a signal transduction pathway relevant to hyperglycemia vascular damage and, hence, may represent a novel therapeutic target against diabetic vascular complications. ..
- 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, it was recently suggested that p66Shc, which is an adaptor molecule of the IGF-I receptor, might play a critical role in this synergistic effect...