{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:23:00Z","timestamp":1779344580212,"version":"3.51.4"},"reference-count":55,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[1998,2,1]],"date-time":"1998-02-01T00:00:00Z","timestamp":886291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Opinion in Genetics & Development"],"published-print":{"date-parts":[[1998,2]]},"DOI":"10.1016\/s0959-437x(98)80062-2","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T23:59:40Z","timestamp":1027641580000},"page":"55-62","source":"Crossref","is-referenced-by-count":591,"title":["Mechanism of activation and function of protein kinase B"],"prefix":"10.1016","volume":"8","author":[{"given":"Dario R","family":"Alessi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/S0959-437X(98)80062-2_BIB1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1432-1033.1991.tb16305.x","article-title":"Molecular-cloning and characterization of a novel putative protein-serine kinase related to the cAMP-dependent and protein-kinase-C families","volume":"201","author":"Coffer","year":"1991","journal-title":"Eur J Biochem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB2","first-page":"244","article-title":"A retroviral oncogene Akt, encoding a serine-threonine kinase containing an SH2-like region","volume":"254","author":"Belacossa","year":"1991","journal-title":"Science"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB3","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1073\/pnas.88.10.4171","article-title":"Molecular cloning and identification of a serine threonine protein-kinase of the 2nd-messenger subfamily","volume":"88","author":"Jones","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB4","doi-asserted-by":"crossref","first-page":"9267","DOI":"10.1073\/pnas.89.19.9267","article-title":"Akt2, a putative oncogene encoding a member of a subfamily of protein-serine threonine kinases, is amplified in human ovarian carcinomas","volume":"89","author":"Cheng","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB5","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1006\/bbrc.1995.2654","article-title":"Molecular-cloning and characterization of a new member of the RAC protein-kinase family \u2014 association of the Pleckstrin homology domain of 3 types of RAC protein-kinase with protein-kinase-C subspecies and \u03b2\u03b3-subunits of G-protein-kinase-C subspecies and bg-subunits of G-proteins","volume":"216","author":"Konishi","year":"1995","journal-title":"Biochem Biophys Res Comm"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0092-8674(00)81022-3","article-title":"PH domains: diverse sequences with a common fold recruit signalling molecules to the cell surface","volume":"85","author":"Lemmon","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/bies.950180109","article-title":"The pleckstrin-homolgy domain, an intrguing multifunctional protein module","volume":"18","author":"Shaw","year":"1996","journal-title":"Bioessays"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB8","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/0092-8674(95)90534-0","article-title":"The protein-kinase encoded by the Akt protooncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase","volume":"81","author":"Franke","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB9","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/376599a0","article-title":"Protein-kinase-B (c-Akt) in phosphatidylinositol-3-OH kinase signal-transduction","volume":"376","author":"Burgering","year":"1995","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB10","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1002\/j.1460-2075.1995.tb00103.x","article-title":"Insulin stimulates the kinase-activity of RAC-PK, a pleckstrin-homology domain-containing Ser\/Thr kinase","volume":"14","author":"Kohn","year":"1995","journal-title":"EMBO J"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB11","article-title":"Activation of the PKB\u03b2 and PKB\u03b3 isoforms by insulin in vivo and PDK1 in vitro: comparison with PKB\u03b1","author":"Walker","year":"1998","journal-title":"Biochem J"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB12","first-page":"272","article-title":"Phosphoinositide 3 kinases: a conserved family of signal transducers","volume":"22","author":"Vanhaesbroeck","year":"1997","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB13","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0968-0004(97)01120-1","article-title":"Inositol lipid 5-phosphatases \u2014 traffic signals and signal traffic","volume":"22","author":"Woscholski","year":"1997","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB14","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1042\/bj3150709","article-title":"Specific binding of the Akt-1 protein-kinase to phosphatidylinositol, 3,4,5-trisphosphate without subsequent activation","volume":"315","author":"James","year":"1996","journal-title":"Biochem J"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB15","doi-asserted-by":"crossref","first-page":"8474","DOI":"10.1074\/jbc.272.13.8474","article-title":"High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin-homology domain of RAC\/Protein kinase B and their influence on the kinase activity","volume":"272","author":"Frech","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB16","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1128\/MCB.17.1.338","article-title":"A specific product of phosphatidyinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain","volume":"17","author":"Klippel","year":"1997","journal-title":"Mol Cell Biol"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB17","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1126\/science.275.5300.665","article-title":"Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate","volume":"275","author":"Franke","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB18_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0960-9822(06)00122-9","article-title":"Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B \u03b1","volume":"7","author":"Alessi","year":"1997","journal-title":"Curr Biol"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB19_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1126\/science.277.5325.567","article-title":"Dual role of phosphatidyinositiol-3,4,5-trisphosphate in the activation of protein kinase B","volume":"277","author":"Stokoe","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB20_1","doi-asserted-by":"crossref","first-page":"6541","DOI":"10.1002\/j.1460-2075.1996.tb01045.x","article-title":"Mechanism of activation of protein kinase B by insulin and IGF1","volume":"15","author":"Alessi","year":"1996","journal-title":"EMBO J"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB21","doi-asserted-by":"crossref","first-page":"21920","DOI":"10.1074\/jbc.271.36.21920","article-title":"Akt, a pleckstrin homology domain-containing kinase, is activated primarily by phosphorylation","volume":"271","author":"Kohn","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB22_1","doi-asserted-by":"crossref","first-page":"31324","DOI":"10.1074\/jbc.272.50.31515","article-title":"Role of translocation in the activation and function of protein kinase B","volume":"272","author":"Andjelkovic","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB23","doi-asserted-by":"crossref","first-page":"30491","DOI":"10.1074\/jbc.272.48.30491","article-title":"Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase B\u03b2","volume":"272","author":"Meier","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB24_1","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/S0960-9822(06)00336-8","article-title":"3-phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase","volume":"7","author":"Alessi","year":"1997","journal-title":"Curr Biol"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB25","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1073\/pnas.94.8.3627","article-title":"Transduction of interleukin-2 anti-apoptotic and proliferative signals via Akt protein kinase","volume":"94","author":"Ahmed","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB26","doi-asserted-by":"crossref","first-page":"21520","DOI":"10.1074\/jbc.272.34.21520","article-title":"Regulation of protein kinase B in rat adipocytes by insulin, vanadate, and peroxovanadate \u2014 membrane translocation in response to peroxovanadate","volume":"272","author":"Wijkander","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB27","doi-asserted-by":"crossref","first-page":"28495","DOI":"10.1074\/jbc.270.48.28495","article-title":"Protein-kinase-C structure, function and regulation","volume":"270","author":"Newton","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB28","doi-asserted-by":"crossref","first-page":"5313","DOI":"10.1128\/MCB.16.10.5313","article-title":"The P160 RHOA-binding kinase ROK-\u03b1 is a member of a kinase family and is involved in the reorganization of the cytoskeleton","volume":"16","author":"Leung","year":"1996","journal-title":"Mol Cell Biol"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB29","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0014-5793(97)00323-2","article-title":"The modular phosphorylation and activation of p70(S6K)","volume":"410","author":"Pullen","year":"1997","journal-title":"FEBS Lett"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB30","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/369411a0","article-title":"Requirement for Ras in Raf activation is overcome by targeting RAF to the plasma-membrane","volume":"369","author":"Leevers","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB31_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0960-9822(98)70037-5","article-title":"3-phosphoinositide dependent protein kinase 1 (PDK1) phosphorylates and activates the p70S6 kinase in vivo and in vitro","volume":"8","author":"Alessi","year":"1998","journal-title":"Curr Biol"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB32","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0014-5793(96)01370-1","article-title":"Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase-1 and p70S6 kinase","volume":"399","author":"Alessi","year":"1996","journal-title":"FEBS Lett"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB33","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/0092-8674(92)90643-Q","article-title":"Rapamycin-FKBP specifically blocks growth-dependent activation of and signalling by the 70 KD S6 protein-kinases","volume":"69","author":"Chung","year":"1992","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB34","doi-asserted-by":"crossref","first-page":"27489","DOI":"10.1074\/jbc.270.46.27489","article-title":"PD-098059 is a specific inhibitor of the activation of mitogen-activated protein-kinase in vitro and in vivo","volume":"270","author":"Alessi","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB35","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/378785a0","article-title":"Inhibition of glycogen-synthase kinase-3 by insulin is mediated by protein-kinase B","volume":"378","author":"Cross","year":"1995","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB36","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0014-5793(97)01235-0","article-title":"Further evidence that the inhibition of glycogen synthase kinase-3\u03b2 by IGF-1 is mediated by PDK1\/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216","volume":"416","author":"Shaw","year":"1997","journal-title":"FEBS Lett"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0014-5793(97)00490-0","article-title":"PDK1, the missing link in insulin signal transduction?","volume":"410","author":"Cohen","year":"1997","journal-title":"FEBS Lett"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB38","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0014-5793(97)01548-2","article-title":"Regulation of eukaryotic initiation factor eIF 2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin","volume":"421","author":"Welsh","year":"1998","journal-title":"FEBS Lett"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB39_1","doi-asserted-by":"crossref","first-page":"17269","DOI":"10.1074\/jbc.272.28.17269","article-title":"Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase-B and other protein kinases of the insulin signalling cascades","volume":"272","author":"Deprez","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB40","doi-asserted-by":"crossref","first-page":"31372","DOI":"10.1074\/jbc.271.49.31372","article-title":"Expression of a constitutively active Akt Ser\/Thr kinase in 3T3-L1 adipocytes stimulates glucose-uptake and glucose-transporter-4 tanslocation","volume":"271","author":"Kohn","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB41","article-title":"Protein kinase B mediates the insulin induced increase in glucose and amino acid uptake in L6 myotubes","author":"Hajduch","year":"1998","journal-title":"Diabetes"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB42","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1210\/en.138.8.3559","article-title":"A constitutively active version of the Ser\/Thr kinase Akt induces production of the ob gene product, leptin, in 3T3-L1 adipocytes","volume":"183","author":"Barthel","year":"1997","journal-title":"Endocrinol"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB43","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1073\/pnas.93.8.3636","article-title":"Amplification of Akt2 in human pancreatic-cancer cells and inhibition of Akt2 expression and tumorigenicity by antisense RNA","volume":"93","author":"Cheng","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB44","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/ijc.2910640412","article-title":"Molecular alterations of the Akt2 oncogene in ovarian and breast carcinomas","volume":"64","author":"Bellacosa","year":"1995","journal-title":"Intl J Cancer"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB45_1","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1128\/MCB.17.3.1595","article-title":"Anti-apoptotic signalling by the insulin-like growth factor receptor, phosphatidylinositol 3-kinase and Akt","volume":"17","author":"Kulik","year":"1997","journal-title":"Mol Cell Biol"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB46_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1126\/science.275.5300.661","article-title":"Regulation of neuronal survival by the Serine-Threonine protein kinase Akt","volume":"275","author":"Dudek","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB47_1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/385544a0","article-title":"Suppression of c-Myc-Induced apoptosis by Ras signalling through PI(3)K and PKB","volume":"385","author":"Kauffmann","year":"1997","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB48_1","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1093\/emboj\/16.10.2783","article-title":"Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B\/Akt cellular survival pathway","volume":"16","author":"Khwaja","year":"1997","journal-title":"EMBO J"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB49","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1126\/science.276.5320.1848","article-title":"Transformation of chicken cells by the gene encoding the catalytic subunit of PI3-kinase","volume":"276","author":"Chang","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB50_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0092-8674(00)80405-5","article-title":"Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery","volume":"91","author":"Datta","year":"1997","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB51","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1126\/science.278.5338.687","article-title":"Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt","volume":"278","author":"DelPeso","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB52_1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0092-8674(00)81382-3","article-title":"Serine phosphorylation of death agonist bad in response to survival factor results in binding to 14-3-3 not BCL-X(L)","volume":"87","author":"Zha","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB53","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1074\/jbc.273.3.1496","article-title":"Identification of the regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1\u03b1\/p90Rsk that are inducible by MAPK","volume":"273","author":"Dalby","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB54","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1126\/science.279.5351.710","article-title":"Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-triphosphate-dependent activation of protein kinase B","volume":"279","author":"Stephens","year":"1998","journal-title":"Science"},{"key":"10.1016\/S0959-437X(98)80062-2_BIB55","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1126\/science.279.5351.707","article-title":"Phosphorylation and activation of P70S6K by PDK1","volume":"279","author":"Pullen","year":"1998","journal-title":"Science"}],"container-title":["Current Opinion in Genetics & Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X98800622?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X98800622?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T07:32:59Z","timestamp":1580887979000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959437X98800622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,2]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1998,2]]}},"alternative-id":["S0959437X98800622"],"URL":"https:\/\/doi.org\/10.1016\/s0959-437x(98)80062-2","relation":{},"ISSN":["0959-437X"],"issn-type":[{"value":"0959-437X","type":"print"}],"subject":[],"published":{"date-parts":[[1998,2]]}}}