Artículo

Risso, G.; Blaustein, M.; Pozzi, B.; Mammi, P.; Srebrow, A. "Akt/PKB: One kinase, many modifications" (2015) Biochemical Journal. 468(2):203-214
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Abstract:

Akt/PKB, a serine/threonine kinase member of the AGC family of proteins, is involved in the regulation of a plethora of cellular processes triggered by a wide diversity of extracellular signals and is thus considered a key signalling molecule in higher eukaryotes. Deregulation of Akt signalling is associated with a variety of human diseases, revealing Akt-dependent pathways as an attractive target for therapeutic intervention. Since its discovery in the early 1990s, a large body of work has focused on Akt phosphorylation of two residues, Thr308 and Ser473 , and modification of these two sites has been established as being equivalent to Akt activation. More recently, Akt has been identified as a substrate for many different posttranslational modifications, including not only phosphorylation of other residues, but also acetylation, glycosylation, oxidation, ubiquitination and SUMOylation. These modifications could provide additional regulatory steps for fine-tuning Akt function, Akt trafficking within the cell and/or for determining the substrate specificity of this signalling molecule. In the present review, we provide an overview of these different post-translational modifications identified for Akt, focusing on their consequences for this kinase activity. © The Authors Journal compilation © 2015 Biochemical Society.

Registro:

Documento: Artículo
Título:Akt/PKB: One kinase, many modifications
Autor:Risso, G.; Blaustein, M.; Pozzi, B.; Mammi, P.; Srebrow, A.
Filiación:Instituto de Fisiología, Biología Molecular Y Neurociencias (IFIBYNE, UBA-CONICET), Ciudad Universitaria, Pabell ón 2, Buenos Aires, C1428EHA, Argentina
Palabras clave:Akt; Post-translational modification; Protein function; Protein kinase B; Signal transduction; cysteine; deubiquitinase; lysine; protein kinase B; serine; threonine; tyrosine; protein kinase B; amino acid sequence; down regulation; enzyme activity; enzyme glycosylation; enzyme metabolism; enzyme phosphorylation; enzyme regulation; enzyme specificity; human; nonhuman; priority journal; protein acetylation; protein degradation; protein function; protein processing; proteomics; Review; signal transduction; sumoylation; ubiquitination; animal; metabolism; protein processing; Eukaryota; Animals; Humans; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt
Año:2015
Volumen:468
Número:2
Página de inicio:203
Página de fin:214
DOI: http://dx.doi.org/10.1042/BJ20150041
Título revista:Biochemical Journal
Título revista abreviado:Biochem. J.
ISSN:02646021
CODEN:BIJOA
CAS:cysteine, 4371-52-2, 52-89-1, 52-90-4; lysine, 56-87-1, 6899-06-5, 70-54-2; protein kinase B, 148640-14-6; serine, 56-45-1, 6898-95-9; threonine, 36676-50-3, 72-19-5; tyrosine, 16870-43-2, 55520-40-6, 60-18-4; Proto-Oncogene Proteins c-akt
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v468_n2_p203_Risso

Referencias:

  • Clark, A.R., Toker, A., Signalling specificity in the Akt pathway in breast cancer (2014) Biochem. Soc. Trans., 42, pp. 1349-1355. , CrossRef PubMed
  • Cheung, M., Testa, J.R., Diverse mechanisms of AKT pathway activation in human malignancy (2013) Curr. Cancer Drug Targets, 13, pp. 234-244. , CrossRef PubMed
  • Altomare, D.A., Testa, J.R., Perturbations of the AKT signaling pathway in human cancer (2005) Oncogene, 24, pp. 7455-7464. , CrossRef PubMed
  • Bellacosa, A., Kumar, C.C., Di Cristofano, A., Testa, J.R., Activation of AKT kinases in cancer: Implications for therapeutic targeting (2005) Adv. Cancer Res., 94, pp. 29-86. , CrossRef PubMed
  • Hers, I., Vincent, E.E., Tavar É, J.M., Akt signalling in health and disease (2011) Cell. Signal., 23, pp. 1515-1527. , CrossRef PubMed
  • Manning, B.D., Cantley, L.C., AKT/PKB signaling: Navigating downstream (2007) Cell, 129, pp. 1261-1274. , CrossRef PubMed
  • Santi, S.A., Lee, H., The Akt isoforms are present at distinct subcellular locations (2010) Am. J. Physiol. Cell Physiol., 298, pp. C580-C591. , CrossRef PubMed
  • Mahajan, K., Mahajan, N.P., PI3K-independent AKT activation in cancers: A treasure trove for novel therapeutics (2012) J. Cell. Physiol., 227, pp. 3178-3184. , CrossRef PubMed
  • Hanada, M., Feng, J., Hemmings, B.A., Structure, regulation and function of PKB/AKT: A major therapeutic target (2004) Biochim. Biophys. Acta, 1697, pp. 3-16. , CrossRef PubMed
  • Huber, M., Helgason, C.D., Damen, J.E., Scheid, M., Duronio, V., Liu, L., Ware, M.D., Krystal, G., The role of SHIP in growth factor induced signalling (1999) Prog. Biophys. Mol. Biol., 71, pp. 423-434. , CrossRef PubMed
  • Rohrschneider, L.R., Fuller, J.F., Wolf, I., Liu, Y., Lucas, D.M., Structure, function, and biology of SHIP proteins (2000) Genes Dev, 14, pp. 505-520. , PubMed
  • Gao, T., Furnari, F., Newton, A.C., PHLPP: A phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth (2005) Mol. Cell, 18, pp. 13-24. , CrossRef PubMed
  • Andjelkovic, M., Jakubowicz, T., Cron, P., Ming, X.F., Han, J.W., Hemmings, B.A., Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors (1996) Proc. Natl. Acad. Sci. U.S.A., 93, pp. 5699-5704. , CrossRef PubMed
  • Alessi, D.R., Deak, M., Casamayor, A., Caudwell, F.B., Morrice, N., Norman, D.G., Gaffney, P., Harbison, D., 3-Phosphoinositide-dependent protein kinase-1 (PDK1): Structural and functional homology with the Drosophila DSTPK61 kinase (1997) Curr. Biol., 7, pp. 776-789. , CrossRef PubMed
  • Sarbassov, D.D., Guertin, D.A., Ali, S.M., Sabatini, D.M., Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex (2005) Science, 307, pp. 1098-1101. , CrossRef PubMed
  • Alessi, D.R., Andjelkovic, M., Caudwell, B., Cron, P., Morrice, N., Cohen, P., Hemmings, B.A., Mechanism of activation of protein kinase B by insulin and IGF-1 (1996) EMBO J, 15, pp. 6541-6551. , PubMed
  • Liao, Y., Hung, M.C., Physiological regulation of Akt activity and stability (2010) Am. J. Transl. Res., 2, pp. 19-42. , PubMed
  • Kohn, A.D., Takeuchi, F., Roth, R.A., Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation (1996) J. Biol. Chem., 271, pp. 21920-21926. , CrossRef PubMed
  • Bellacosa, A., Chan, T.O., Ahmed, N.N., Datta, K., Malstrom, S., Stokoe, D., McCormick, F., Tsichlis, P., Akt activation by growth factors is a multiple-step process: The role of the PH domain (1998) Oncogene, 17, pp. 313-325. , CrossRef PubMed
  • Liao, Y., Wei, Y., Zhou, X., Yang, J.-Y., Dai, C., Chen, Y.-J., Agarwal, N.K., Yu, D., Peptidyl-prolyl cis/trans isomerase Pin1 is critical for the regulation of PKB/Akt stability and activation phosphorylation (2009) Oncogene, 28, pp. 2436-2445. , CrossRef PubMed
  • Conus, N.M., Hannan, K.M., Cristiano, B.E., Hemmings, B.A., Pearson, R.B., Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase (2002) J. Biol. Chem., 277, pp. 38021-38028. , CrossRef PubMed
  • Di Maira, G., Salvi, M., Arrigoni, G., Marin, O., Sarno, S., Brustolon, F., Pinna, L.A., Ruzzene, M., Protein kinase CK2 phosphorylates and upregulates Akt/PKB (2005) Cell Death Differ, 12, pp. 668-677. , CrossRef PubMed
  • Di Maira, G., Brustolon, F., Pinna, L.A., Ruzzene, M., Dephosphorylation and inactivation of Akt/PKB is counteracted by protein kinase CK2 in HEK 293T cells (2009) Cell. Mol. Life Sci., 66, pp. 3363-3373. , CrossRef PubMed
  • Gulen, M.F., Bulek, K., Xiao, H., Yu, M., Gao, J., Sun, L., Beurel, E., DiCorleto, P.E., Inactivation of the enzyme GSK3α by the kinase IKKi promotes AKT-mTOR signaling pathway that mediates interleukin-1-induced Th17 cell maintenance (2012) Immunity, 37, pp. 800-812. , CrossRef PubMed
  • Chan, T.O., Rittenhouse, S.E., Tsichlis, P.N., AKT/PKB and other D3 phosphoinositide-regulated kinases: Kinase activation by phosphoinositide-dependent phosphorylation (1999) Annu. Rev. Biochem., 68, pp. 965-1014. , CrossRef PubMed
  • Chan, T.O., Tsichlis, P.N., PDK2: A complex tail in one Akt (2001) Sci. STKE, 2001, p. pe1. , PubMed
  • Alessi, D.R., Pearce, L.R., García-Martínez, J.M., New insights into mTOR signaling: MTORC2 and beyond (2009) Sci. Signal., 2, p. pe27. , CrossRef PubMed
  • Ikenoue, T., Inoki, K., Yang, Q., Zhou, X., Guan, K.-L., Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling (2008) EMBO J, 27, pp. 1919-1931. , CrossRef PubMed
  • Facchinetti, V., Ouyang, W., Wei, H., Soto, N., Lazorchak, A., Gould, C., Lowry, C., Miao, R.Q., The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C (2008) EMBO J, 27, pp. 1932-1943. , CrossRef PubMed
  • Oh, W.J., Wu, C.C., Kim, S.J., Facchinetti, V., Julien, L.A., Finlan, M., Roux, P.P., Jacinto, E., MTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide (2010) EMBO J, 29, pp. 3939-3951. , CrossRef PubMed
  • Shao, Z., Bhattacharya, K., Hsich, E., Park, L., Walters, B., Germann, U., Wang, Y.M., Kuida, K., C-Jun N-terminal kinases mediate reactivation of Akt and cardiomyocyte survival after hypoxic injury in vitro and in vivo (2006) Circ. Res., 98, pp. 111-118. , CrossRef PubMed
  • Wei, J., Wang, W., Chopra, I., Li, H.F., Dougherty, C.J., Adi, J., Adi, N., Webster, K.A., C-Jun N-terminal kinase (JNK-1) confers protection against brief but not extended ischemia during acute myocardial infarction (2011) J. Biol. Chem., 286, pp. 13995-14006. , CrossRef PubMed
  • Liu, P., Begley, M., Michowski, W., Inuzuka, H., Ginzberg, M., Gao, D., Tsou, P., Kim, B.M., Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus (2014) Nature, 508, pp. 541-545. , CrossRef PubMed
  • Liu, P., Wang, Z., Wei, W., Phosphorylation of Akt at the C-terminal tail triggers Akt activation (2014) Cell Cycle, 13, pp. 2162-2164. , CrossRef PubMed
  • Mahajan, K., Coppola, D., Challa, S., Fang, B., Chen, Y.A., Zhu, W., Lopez, A.S., Rivera, C., Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation (2010) PLoS ONE, 5, p. e9646. , CrossRef PubMed
  • Datta, K., Bellacosaf, A., Chan, T.O., Tsichlis, P.N., Akt is a direct target of the phosphatidylinositol 3-kinase: Activation by growth factors, v-src and v-Ha-ras, in Sf9 and mammalian cells (1996) J. Biol. Chem., 271, pp. 30835-30839. , CrossRef PubMed
  • Wong, B.R., Besser, D., Kim, N., Arron, J.R., Vologodskaia, M., Hanafusa, H., Choi, Y., TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src (1999) Mol. Cell, 4, pp. 1041-1049
  • Chen, R., Kim, O., Yang, J., Sato, K., Eisenmann, K.M., McCarthy, J., Chen, H., Qiu, Y., Regulation of Akt/PKB activation by tyrosine phosphorylation (2001) J. Biol. Chem., 276, pp. 31858-31862. , CrossRef PubMed
  • Jiang, T., Qiu, Y., Interaction between Src and a C-terminal proline-rich motif of Akt is required for Akt activation (2003) J. Biol. Chem., 278, pp. 15789-15793. , CrossRef PubMed
  • Luan, B., Zhao, J., Wu, H., Duan, B., Shu, G., Wang, X., Li, D., Pei, G., Deficiency of a β -arrestin-2 signal complex contributes to insulin resistance (2009) Nature, 457, pp. 1146-1149. , CrossRef PubMed
  • Zheng, Y., Peng, M., Wang, Z., Asara, J.M., Tyner, A.L., Protein tyrosine kinase 6 directly phosphorylates AKT and promotes AKT activation in response to epidermal growth factor (2010) Mol. Cell. Biol., 30, pp. 4280-4292. , CrossRef PubMed
  • Balendran, A., Casamayor, A., Deak, M., Paterson, A., Gaffney, P., Currie, R., Downes, C.P., Alessi, D.R., PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 (1999) Curr. Biol., 9, pp. 393-404. , CrossRef PubMed
  • Guo, J.P., Coppola, D., Cheng, J.Q., IKBKE protein activates Akt independent of phosphatidylinositol 3-kinase/PDK1/mTORC2 and the pleckstrin homology domain to sustain malignant transformation (2011) J. Biol. Chem., 286, pp. 37389-37398. , CrossRef PubMed
  • Joung, S.M., Park, Z.-Y., Rani, S., Takeuchi, O., Akira, S., Lee, J.Y., Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1 (2011) J. Immunol., 186, pp. 499-507. , CrossRef PubMed
  • Choudhary, C., Kumar, C., Gnad, F., Nielsen, M.L., Rehman, M., Walther, T.C., Olsen, J.V., Mann, M., Lysine acetylation targets protein complexes and co-regulates major cellular functions (2009) Science, 325, pp. 834-840. , CrossRef PubMed
  • Milne, J.C., Lambert, P.D., Schenk, S., Carney, D.P., Smith, J.J., Gagne, D.J., Jin, L., Vu, C.B., Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes (2007) Nature, 450, pp. 712-716. , CrossRef PubMed
  • Sundaresan, N.R., Pillai, V.B., Wolfgeher, D., Samant, S., Vasudevan, P., Parekh, V., Raghuraman, H., Gupta, M.P., The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy (2011) Sci. Signal., 4, p. ra46. , CrossRef PubMed
  • Chung, H.S., Wang, S.-B., Venkatraman, V., Murray, C.I., Van Eyk, J.E., Cysteine oxidative posttranslational modifications: Emerging regulation in the cardiovascular system (2013) Circ. Res., 112, pp. 382-392. , CrossRef PubMed
  • Finkel, T., Signal transduction by reactive oxygen species (2011) J. Cell Biol., 194, pp. 7-15. , CrossRef PubMed
  • Wani, R., Qian, J., Yin, L., Bechtold, E., King, S.B., Poole, L.B., Paek, E., Furdui, C.M., Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species (2011) Proc. Natl. Acad. Sci. U.S.A., 108, pp. 10550-10555. , CrossRef PubMed
  • Wani, R., Bharathi, N.S., Field, J., Tsang, A.W., Furdui, C.M., Oxidation of Akt2 kinase promotes cell migration and regulates G<inf>1</inf> -S transition in the cell cycle (2011) Cell Cycle, 10, pp. 3263-3268. , CrossRef PubMed
  • Hart, G.W., Slawson, C., Ramirez-Correa, G., Lagerlof, O., Cross talk between O-GlcNAcylation and phosphorylation: Roles in signaling, transcription, and chronic disease (2011) Annu. Rev. Biochem., 80, pp. 825-858. , CrossRef PubMed
  • Zeidan, Q., Hart, G.W., The intersections between O-GlcNAcylation and phosphorylation: Implications for multiple signaling pathways (2010) J. Cell Sci., 123, pp. 13-22. , CrossRef PubMed
  • Park, S.Y., Ryu, J., Lee, W., O-GlcNAc modification on IRS-1 and Akt2 by PUGNAc inhibits their phosphorylation and induces insulin resistance in rat primary adipocytes (2005) Exp. Mol. Med., 37, pp. 220-229. , CrossRef PubMed
  • Gandy, J.C., Rountree, A.E., Bijur, G.N., Akt1 is dynamically modified with O-GlcNAc following treatments with PUGNAc and insulin-like growth factor-1 (2006) FEBS Lett, 580, pp. 3051-3058. , CrossRef PubMed
  • Whelan, S.A., Lane, M.D., Hart, G.W., Regulation of the O-linked β -N-acetylglucosamine transferase by insulin signaling (2008) J. Biol. Chem., 283, pp. 21411-21417. , CrossRef PubMed
  • Ball, L.E., Berkaw, M.N., Buse, M.G., Identification of the major site of O-linked β -N-acetylglucosamine modification in the C terminus of insulin receptor substrate-1 (2006) Mol. Cell. Proteomics, 5, pp. 313-323. , CrossRef PubMed
  • Klein, A.L., Berkaw, M.N., Buse, M.G., Ball, L.E., O-linked N-acetylglucosamine modification of insulin receptor substrate-1 occurs in close proximity to multiple SH2 domain binding motifs (2009) Mol. Cell. Proteomics, 8, pp. 2733-2745. , CrossRef PubMed
  • Vosseller, K., Wells, L., Lane, M.D., Hart, G.W., Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes (2002) Proc. Natl. Acad. Sci. U.S.A., 99, pp. 5313-5318. , CrossRef PubMed
  • Yang, X., Ongusaha, P.P., Miles, P.D., Havstad, J.C., Zhang, F., So, W.V., Kudlow, J.E., Field, S.J., Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance (2008) Nature, 451, pp. 964-969. , CrossRef PubMed
  • Wang, S., Huang, X., Sun, D., Xin, X., Pan, Q., Peng, S., Liang, Z., Jiang, H., Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt signaling (2012) PLoS ONE, 7, p. e37427. , CrossRef PubMed
  • Kang, E.-S., Han, D., Park, J., Kwak, T.K., Oh, M.-A., Lee, S.-A., Choi, S., Lee, J.W., O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic β cells (2008) Exp. Cell Res., 314, pp. 2238-2248. , CrossRef PubMed
  • Heath, J.M., Sun, Y., Yuan, K., Bradley, W.E., Litovsky, S., Dell'Italia, L.J., Chatham, J.C., Chen, Y., Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus (2014) Circ. Res., 114, pp. 1094-1102. , CrossRef PubMed
  • Finley, D., Recognition and processing of ubiquitin-protein conjugates by the proteasome (2009) Annu. Rev. Biochem., 78, pp. 477-513. , CrossRef PubMed
  • Basso, A.D., Solit, D.B., Chiosis, G., Giri, B., Tsichlis, P., Rosen, N., Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function (2002) J. Biol. Chem., 277, pp. 39858-39866. , CrossRef PubMed
  • Xiang, T., Ohashi, A., Huang, Y., Pandita, T.K., Ludwig, T., Powell, S.N., Yang, Q., Negative regulation of AKT activation by BRCA1 (2008) Cancer Res, 68, pp. 10040-10044. , CrossRef PubMed
  • Dickey, C.A., Koren, J., Zhang, Y.-J., Xu, Y.-F., Jinwal, U.K., Birnbaum, M.J., Monks, B., Patterson, C., Akt and CHIP coregulate tau degradation through coordinated interactions (2008) Proc. Natl. Acad. Sci. U.S.A., 105, pp. 3622-3627. , CrossRef PubMed
  • Su, C.H., Wang, C.Y., Lan, K.H., Li, C.P., Chao, Y., Lin, H.C., Lee, S.D., Lee, W.P., Akt phosphorylation at Thr308 and Ser473 is required for CHIP-mediated ubiquitination of the kinase (2011) Cell. Signal., 23, pp. 1824-1830. , CrossRef PubMed
  • Suizu, F., Hiramuki, Y., Okumura, F., Matsuda, M., Okumura, A.J., Hirata, N., Narita, M., Bohgaki, M., The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt (2009) Dev. Cell, 17, pp. 800-810. , CrossRef PubMed
  • Bae, S., Kim, S.Y., Jung, J.H., Yoon, Y., Cha, H.J., Lee, H., Kim, K., Um, H.D., Akt is negatively regulated by the MULAN E3 ligase (2012) Cell Res., 22, pp. 873-885. , CrossRef PubMed
  • Yang, W.-L., Wang, J., Chan, C.-H., Lee, S.-W., Campos, A.D., Lamothe, B., Hur, L., Darnay, B.G., The E3 ligase TRAF6 regulates Akt ubiquitination and activation (2009) Science, 325, pp. 1134-1138. , CrossRef PubMed
  • Chan, C.H., Li, C.F., Yang, W.L., Gao, Y., Lee, S.W., Feng, Z., Huang, H.Y., Shao, Y., The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis (2012) Cell, 149, pp. 1098-1111. , CrossRef PubMed
  • Fan, C.-D., Lum, M.A., Xu, C., Black, J.D., Wang, X., Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4-1, in the insulin-like growth factor-1 response (2013) J. Biol. Chem., 288, pp. 1674-1684. , CrossRef PubMed
  • Lim, J.H., Jono, H., Komatsu, K., Woo, C.-H., Lee, J., Miyata, M., Matsuno, T., Zhang, W., CYLD negatively regulates transforming growth factor-β -signalling via deubiquitinating Akt (2012) Nat. Commun., 3, p. 771. , CrossRef PubMed
  • Yang, W.-L., Jin, G., Li, C.-F., Jeong, Y.S., Moten, A., Xu, D., Feng, Z., Darnay, B., Cycles of ubiquitination and deubiquitination critically regulate growth factor-mediated activation of Akt signaling (2013) Sci. Signal., 6, p. ra3. , PubMed
  • Geiss-Friedlander, R., Melchior, F., Concepts in sumoylation: A decade on (2007) Nat. Rev. Mol. Cell Biol., 8, pp. 947-956. , CrossRef PubMed
  • Bernassola, F., Karin, M., Ciechanover, A., Melino, G., The HECT family of E3 ubiquitin ligases: Multiple players in cancer development (2008) Cancer Cell, 14, pp. 10-21. , CrossRef PubMed
  • Deshaies, R.J., Joazeiro, C.A., RING domain E3 ubiquitin ligases (2009) Annu. Rev. Biochem., 78, pp. 399-434. , CrossRef PubMed
  • Li, R., Wei, J., Jiang, C., Liu, D., Deng, L., Zhang, K., Wang, P., Akt SUMOylation regulates cell proliferation and tumorigenesis (2013) Cancer Res, 73, pp. 5742-5753. , CrossRef PubMed
  • Risso, G., Pelisch, F., Pozzi, B., Mammi, P., Blaustein, M., Colman-Lerner, A., Srebrow, A., Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle (2013) Cell Cycle, 12, pp. 3165-3174. , CrossRef PubMed
  • Hendriks, I.A., D'Souza, R.C.J., Yang, B., Verlaan-de Vries, M., Mann, M., Vertegaal, A.C.O., Uncovering global SUMOylation signaling networks in a site-specific manner (2014) Nat. Struct. Mol. Biol., 21, pp. 927-936. , CrossRef PubMed
  • De La Cruz-Herrera, C.F., Campagna, M., Lang, V., Del Carmen Gonz Ález-Santamaría, J., Marcos-Villar, L., Rodríguez, M.S., Vidal, A., Rivas, C., SUMOylation regulates AKT1 activity (2014) Oncogene, 34, pp. 1-9. , PubMed
  • Huang, J., Yan, J., Zhang, J., Zhu, S., Wang, Y., Shi, T., Zhu, C., Cheng, J., SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane (2012) Nat. Commun., 3, p. 911. , CrossRef PubMed
  • Bassi, C., Ho, J., Srikumar, T., Dowling, R.J.O., Gorrini, C., Miller, S.J., Mak, T.W., Stambolic, V., Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress (2013) Science, 341, pp. 395-399. , CrossRef PubMed
  • Gonzalez-Santamaria, J., Campagna, M., Ortega-Molina, A., Marcos-Villar, L., De La Cruz-Herrera, C.F., Gonzalez, D., Gallego, P., Rodriguez, M.S., Regulation of the tumor suppressor PTEN by SUMO (2012) Cell Death Dis., 3, p. e393. , CrossRef PubMed
  • Psakhye, I., Jentsch, S., Protein group modification and synergy in the SUMO pathway as exemplified in DNA repair (2012) Cell, 151, pp. 807-820. , CrossRef PubMed
  • Flotho, A., Melchior, F., Sumoylation: A regulatory protein modification in health and disease (2013) Annu. Rev. Biochem., 82, pp. 357-385. , CrossRef PubMed
  • Chen, J.-Y., Lin, J.-R., Cimprich, K.A., Meyer, T., A two-dimensional ERK-AKT signaling code for an NGF-triggered cell-fate decision (2012) Mol. Cell, 45, pp. 196-209. , CrossRef PubMed
  • Hosoi, T., Hyoda, K., Okuma, Y., Nomura, Y., Ozawa, K., Akt up- and down-regulation in response to endoplasmic reticulum stress (2007) Brain Res, 1152, pp. 27-31. , CrossRef PubMed
  • Mounir, Z., Krishnamoorthy, J.L., Wang, S., Papadopoulou, B., Campbell, S., Muller, W.J., Hatzoglou, M., Koromilas, A.E., Akt determines cell fate through inhibition of the PERK-eIF2α phosphorylation pathway (2011) Sci. Signal., 4, p. ra62. , CrossRef PubMed
  • Blaustein, M., Pérez-Munizaga, D., Sánchez, M.A., Urrutia, C., Grande, A., Risso, G., Srebrow, A., Colman-Lerner, A., Modulation of the Akt pathway reveals a novel link with PERK/eIF2α, which is relevant during hypoxia (2013) PLoS ONE, 8, p. e69668. , CrossRef PubMed
  • Rajesh, K., Krishnamoorthy, J., Kazimierczak, U., Tenkerian, C., Papadakis, A.I., Wang, S., Huang, S., Koromilas, A.E., Phosphorylation of the translation initiation factor eIF2α at serine 51 determines the cell fate decisions of Akt in response to oxidative stress (2015) Cell Death Dis, 6, p. e1591. , CrossRef PubMed
  • Shaw, J., Kirshenbaum, L.A., Prime time for JNK-mediated Akt reactivation in hypoxia-reoxygenation (2006) Circ. Res., 98, pp. 7-9. , CrossRef PubMed
  • Singh, D.K., Ku, C.-J., Wichaidit, C., Steininger, R.J., Wu, L.F., Altschuler, S.J., Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities (2010) Mol. Syst. Biol., 6, p. 369. , CrossRef PubMed
  • Purvis, J.E., Lahav, G., Encoding and decoding cellular information through signaling dynamics (2013) Cell, 152, pp. 945-956. , CrossRef PubMed
  • Lin, C.H., Liu, S.Y., Lee, E.H., (2015) SUMO Modification of Akt Regulates Global SUMOylation and Substrate SUMOylation Specificity through Akt Phosphorylation of Ubc9 and SUMO1., , Oncogene CrossRef

Citas:

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Risso, G., Blaustein, M., Pozzi, B., Mammi, P. & Srebrow, A. (2015) . Akt/PKB: One kinase, many modifications. Biochemical Journal, 468(2), 203-214.
http://dx.doi.org/10.1042/BJ20150041
---------- CHICAGO ----------
Risso, G., Blaustein, M., Pozzi, B., Mammi, P., Srebrow, A. "Akt/PKB: One kinase, many modifications" . Biochemical Journal 468, no. 2 (2015) : 203-214.
http://dx.doi.org/10.1042/BJ20150041
---------- MLA ----------
Risso, G., Blaustein, M., Pozzi, B., Mammi, P., Srebrow, A. "Akt/PKB: One kinase, many modifications" . Biochemical Journal, vol. 468, no. 2, 2015, pp. 203-214.
http://dx.doi.org/10.1042/BJ20150041
---------- VANCOUVER ----------
Risso, G., Blaustein, M., Pozzi, B., Mammi, P., Srebrow, A. Akt/PKB: One kinase, many modifications. Biochem. J. 2015;468(2):203-214.
http://dx.doi.org/10.1042/BJ20150041