Affinage

AKT1

RAC-alpha serine/threonine-protein kinase · UniProt P31749

Round 2 corrected
Length
480 aa
Mass
55.7 kDa
Annotated
2026-04-28
130 papers in source corpus 55 papers cited in narrative 54 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AKT1 (PKBα) is a central PI3K-effector serine/threonine kinase that transduces growth factor, insulin, and stress signals into phosphorylation of a broad substrate network governing cell survival, metabolism, proliferation, and angiogenesis. Activation requires PH domain-mediated recruitment to the plasma membrane by PtdIns(3,4,5)P3/PtdIns(3,4)P2, followed by phosphorylation at Thr308 by PDK1 and Ser473 primarily by mTORC2 (with context-dependent contributions from DNA-PK, TBK1, PAK1, and ATM), plus tyrosine phosphorylation at Tyr176 by Ack1/Src-family kinases (PMID:7774014, PMID:8978681, PMID:15718470, PMID:11445557, PMID:20333297). Active AKT1 directly phosphorylates GSK3 (glycogen synthesis), BAD and caspase-9 (apoptosis suppression), FoxO transcription factors (pro-apoptotic gene repression), TSC2 and PRAS40 (mTORC1 activation), MDM2 (p53 degradation), eNOS (NO production), Skp2 (cell proliferation), and Girdin (endothelial migration), while its activity is negatively regulated by PTEN-mediated PIP3 dephosphorylation, SHIP-mediated PIP3 hydrolysis, ceramide-activated phosphatase, and caspase-mediated cleavage (PMID:8524413, PMID:9381178, PMID:9812896, PMID:10102273, PMID:12172553, PMID:17277771, PMID:11504915, PMID:10376603, PMID:19270694, PMID:18264090, PMID:9778245, PMID:9852043, PMID:10623893). The somatic gain-of-function mutation E17K in the PH domain constitutively localizes AKT1 to the plasma membrane and is oncogenic, inducing leukemia in mice (PMID:17611497).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Establishing AKT1 as a direct PI3K effector and its first physiological substrate resolved how growth factor signaling was transduced beyond PI3K to metabolic and survival outputs.

    Evidence PH-domain mutants and wortmannin in fibroblasts showed PI3K-dependent AKT activation (PDGF); parallel work demonstrated AKT directly phosphorylates GSK3 downstream of insulin

    PMID:7774014 PMID:8524413

    Open questions at the time
    • Upstream activating kinase(s) for AKT unknown at this point
    • How PIP3 binding translates to kinase activation remained unclear
  2. 1996 High

    Identification of the dual-phosphorylation requirement (Thr308/Ser473) and direct PIP3/PI(3,4)P2 binding via the PH domain defined the activation mechanism and membrane recruitment step.

    Evidence Mutagenesis of Thr308 and Ser473 in 293 cells abolished full activity; surface plasmon resonance quantified submicromolar PH-domain binding to PIP3; myristoylated AKT drove GLUT4 translocation without insulin

    PMID:8645147 PMID:8940145 PMID:8978681

    Open questions at the time
    • Identity of Thr308 kinase (PDK1) not yet published
    • Identity of Ser473 kinase unknown
    • Structural basis of PH-kinase domain autoinhibition unresolved
  3. 1997 High

    Discovery of BAD as a direct AKT substrate established the first molecular mechanism by which AKT suppresses apoptosis.

    Evidence In vitro and in vivo phosphorylation of BAD by AKT at IL-3-responsive sites neutralized BAD pro-apoptotic function

    PMID:9005852 PMID:9381178

    Open questions at the time
    • Whether AKT targets other apoptotic regulators was unknown
    • Relative contribution of BAD phosphorylation versus other survival mechanisms unclear
  4. 1998 High

    Identification of PTEN as the PIP3 phosphatase that antagonizes AKT, and SHIP as a parallel negative regulator, defined the major off-switches for AKT signaling and linked PTEN loss to constitutive AKT activation in cancer.

    Evidence PTEN-null MEFs showed constitutive AKT activity rescued by PTEN re-expression; SHIP-deficient B cells revealed PIP3 as the dominant in vivo AKT activating lipid; AKT also shown to phosphorylate and inactivate caspase-9

    PMID:9778245 PMID:9812896 PMID:9852043

    Open questions at the time
    • Whether PTEN-AKT axis is the sole mechanism of PTEN tumor suppression
    • Context-dependency of SHIP versus PTEN regulation unclear
  5. 1999 High

    Expansion of the AKT substrate repertoire to FoxO transcription factors, eNOS, and the NF-κB pathway (via IKKα) revealed AKT as a hub controlling transcription, vascular tone, and inflammation beyond simple survival signaling.

    Evidence AKT phosphorylated FKHRL1 causing 14-3-3 sequestration; AKT phosphorylated eNOS Ser1177 activating NO production; AKT phosphorylated IKKα Thr23 activating NF-κB; TRAF6/c-Src complex relayed TRANCE signals to AKT in osteoclasts

    PMID:10102273 PMID:10376603 PMID:10485710 PMID:10635328

    Open questions at the time
    • Specificity of AKT isoforms for different substrates not yet addressed
    • In vivo genetic validation of NF-κB pathway limited
  6. 2000 Medium

    Negative regulation of AKT was expanded to include caspase-mediated cleavage and ceramide-activated phosphatase dephosphorylation, revealing feedback loops and stress-dependent inactivation mechanisms.

    Evidence Caspases cleaved AKT between PH and kinase domains generating inactive fragments; C2-ceramide activated CAPP-mediated dephosphorylation at Thr308/Ser473

    PMID:10623893 PMID:10673324

    Open questions at the time
    • Physiological relevance of caspase cleavage versus phosphatase-mediated inactivation in vivo unclear
    • Identity of the ceramide-activated phosphatase not molecularly defined
  7. 2001 High

    AKT-mediated phosphorylation of MDM2 and p27 established direct connections to p53 regulation and cell-cycle control, broadening AKT's oncogenic reach.

    Evidence AKT phosphorylated MDM2 at Ser166/186 promoting nuclear entry and p53 degradation; AKT phosphorylated p27 at Thr157 impairing nuclear import, validated by in vitro import assay and mutagenesis; Src-family tyrosine phosphorylation shown essential for AKT activation

    PMID:11445557 PMID:11504915 PMID:12244302

    Open questions at the time
    • Relative quantitative contribution of MDM2 versus direct FoxO/BAD pathways to AKT-driven survival
    • Whether Src phosphorylation of AKT is permissive or activating
  8. 2002 High

    Identification of TSC2 as a direct AKT substrate that relays signals to mTOR/S6K resolved how insulin/PI3K signaling activates mTORC1-dependent protein synthesis and growth.

    Evidence Two independent groups showed AKT phosphorylates TSC2 at S939/T1462, disrupting TSC1-TSC2 interaction and activating mTOR/S6K1; PTEN-null cells had constitutive TSC2 phosphorylation

    PMID:12150915 PMID:12172553

    Open questions at the time
    • Whether TSC2 phosphorylation is the sole mechanism of mTORC1 activation by AKT
    • Regulatory interplay between TSC2 and other mTOR regulators
  9. 2005 High

    Identification of mTORC2 (rictor-mTOR) as the long-sought Ser473 kinase ('PDK2') resolved a decade-long question and revealed that mTOR functions both upstream and downstream of AKT.

    Evidence Purified mTORC2 phosphorylated AKT Ser473 in vitro; rictor RNAi abolished Ser473 phosphorylation in Drosophila and human cells; ATM and DNA-PK identified as alternative Ser473 kinases in specific contexts

    PMID:15546863 PMID:15718470

    Open questions at the time
    • Context rules determining which kinase phosphorylates Ser473 not systematically defined
    • Whether mTORC2 activity itself is regulated by AKT feedback
  10. 2006 High

    Genetic dissection of mTORC2 subunits (SIN1, mSin1) revealed that Ser473 phosphorylation selectively controls a subset of AKT substrates (FoxO1/3a) but not others (TSC2, GSK3), establishing phosphosite-dependent substrate selectivity.

    Evidence Sin1 knockout eliminated Ser473 phosphorylation; FoxO phosphorylation was lost but TSC2/GSK3 phosphorylation was maintained; prolonged rapamycin disrupted mTORC2 and reduced Ser473 in many cell lines

    PMID:16603397 PMID:16919458 PMID:16962653

    Open questions at the time
    • Full map of Ser473-dependent versus -independent substrates incomplete
    • How mTORC2 itself is activated remained unclear
  11. 2007 High

    PRAS40 was identified as both an AKT substrate and an mTORC1 inhibitor, providing a second parallel mechanism (alongside TSC2) by which AKT activates mTORC1; the oncogenic E17K mutation defined a PIP3-independent activation mechanism relevant to human cancer.

    Evidence AKT phosphorylation of PRAS40 caused 14-3-3 binding and mTORC1 derepression; E17K mutant constitutively localized to plasma membrane and induced leukemia in mice; AKT1 knockout mice showed increased osteoblast apoptosis via FoxO3a/Bim

    PMID:17277771 PMID:17386266 PMID:17611497 PMID:17957242

    Open questions at the time
    • Relative quantitative contributions of TSC2 versus PRAS40 in mTORC1 activation
    • Frequency and clinical significance of E17K across cancer types not fully established at this point
  12. 2008 High

    AKT-mediated phosphorylation of Girdin linked the kinase to VEGF-dependent angiogenesis, and lipid raft nanodomains were shown to facilitate AKT membrane recruitment.

    Evidence Girdin knockout mice had impaired retinal angiogenesis; fluorescence correlation spectroscopy showed raft disruption impaired AKT recruitment

    PMID:18264090 PMID:18641634

    Open questions at the time
    • Whether Girdin is the principal AKT effector in angiogenesis or one of several
    • How raft composition is regulated to tune AKT activation
  13. 2009 High

    The intramolecular PH-kinase domain autoinhibitory interaction was demonstrated by live-cell FRET, explaining how allosteric inhibitors lock AKT in an inactive conformation; Skp2 was identified as a direct AKT substrate linking AKT to ubiquitin-dependent proliferation and migration.

    Evidence FRET/FLIM confirmed PH-kinase closed conformation stabilized by allosteric inhibitor; AKT phosphorylated Skp2 Ser72 promoting SCF activity and cytosolic relocalization; Pin1 shown to regulate AKT stability

    PMID:19166270 PMID:19270694 PMID:19448664

    Open questions at the time
    • Full structural resolution of the autoinhibited conformation at atomic level
    • Whether Pin1-AKT interaction is therapeutically targetable
  14. 2011 High

    TBK1 was identified as a non-canonical AKT kinase capable of phosphorylating both Thr308 and Ser473 at the exocyst, expanding the repertoire of AKT-activating kinases beyond PDK1/mTORC2 to innate immune contexts.

    Evidence In vitro reconstitution with TBK1, TBK1 knockout cells, exocyst co-IP, selective TBK1 inhibitor

    PMID:21329883

    Open questions at the time
    • Quantitative contribution of TBK1 versus mTORC2/PDK1 in physiological settings
    • Whether TBK1-AKT axis operates in non-immune cells
  15. 2020 High

    Systematic substrate profiling with defined phospho-AKT1 variants revealed that Ser473 phosphorylation can both positively and negatively regulate kinase activity in a substrate-dependent manner, overturning the simple model that Ser473 universally enhances activity.

    Evidence Programmed site-specific phosphorylation combined with oriented peptide array libraries covering ~10^11 sequences and 84-substrate peptide panels

    PMID:32350110

    Open questions at the time
    • How substrate-specific effects of Ser473 are integrated in vivo
    • Whether phosphosite-dependent selectivity differs across AKT isoforms

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis and stoichiometry of mTORC2-AKT interaction at membranes, the rules determining which Ser473 kinase (mTORC2, DNA-PK, TBK1, ATM, PAK1) is engaged in a given cell type and stimulus, and whether AKT isoform-specific substrate selectivity can be exploited therapeutically.
  • No high-resolution structure of full-length membrane-bound AKT1 with activating kinase
  • Isoform-specific substrate maps incomplete
  • Quantitative modeling of multi-kinase Ser473 regulation lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 18 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 6 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-5357801 Programmed Cell Death 5 R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2
Partners
GSK3BPDK1PIN1PTENRICTORSIN1TBK1TNK2
Complex memberships
mTORC2 (as substrate)

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 AKT1/PKB is activated downstream of PI3-kinase in response to PDGF; activation requires the pleckstrin homology (PH) domain and is blocked by the PI3K inhibitor wortmannin and dominant-negative Ras, identifying AKT as a novel PI3K target. Kinase activity assays, wortmannin inhibition, dominant-negative Ras expression, PH-domain mutants in fibroblasts Cell High 7774014
1995 AKT/PKB directly phosphorylates and inhibits glycogen synthase kinase-3 (GSK3) in response to insulin, linking PI3K-PKB activation to glycogen synthesis regulation; this effect is blocked by PI3K inhibitors but not by inhibitors of MAPKAP kinase-1 or p70S6K. In vivo phosphorylation assays, kinase inhibitors, immune complex kinase assays in insulin-stimulated cells Nature High 8524413
1996 AKT1 activation by insulin/IGF-1 requires phosphorylation at both Thr308 and Ser473; Thr308 phosphorylation is in the activation loop, Ser473 in the C-terminal hydrophobic motif; both are prevented by wortmannin, and mutation of either residue to Ala abolishes full kinase activity. Site-directed mutagenesis of Thr308 and Ser473, in vitro stoichiometric phosphorylation, transfection into 293 cells, kinase assays The EMBO journal High 8978681
1996 Membrane-targeted (myristoylated) constitutively active AKT stimulates GLUT4 translocation to the plasma membrane and glucose uptake in 3T3-L1 adipocytes independently of insulin, establishing AKT as sufficient to drive glucose transport. Constitutively active myristoylated AKT expression in adipocytes, glucose uptake assay, GLUT4 translocation The Journal of biological chemistry High 8940145
1996 AKT1 specifically binds PtdIns(3,4,5)P3 and PtdIns(3,4)P2 via its PH domain with submicromolar affinity (as measured by surface plasmon resonance); lipid binding alone does not activate AKT1, suggesting PIP3 recruits AKT to the plasma membrane for activation by an upstream kinase. Lipid-binding assays, surface plasmon resonance quantitative binding measurements, L6 myotube fractions The Biochemical journal High 8645147
1997 PtdIns(3,4)P2 directly activates AKT through interaction with the AKT PH domain and facilitates AKT dimerization; mutation of the PH domain prevents PI3K-dependent activation and PtdIns(3,4)P2 binding. In vitro lipid-binding, in vivo activation assays, PH-domain mutants Science High 9005852
1997 AKT directly phosphorylates the pro-apoptotic protein BAD in vivo and in vitro at the same residues phosphorylated in response to IL-3, thereby neutralizing BAD's death-promoting activity downstream of PI3K. In vitro kinase assay with recombinant proteins, in vivo phosphorylation in cells expressing active/inactive Akt Science High 9381178
1998 PTEN dephosphorylates PtdIns(3,4,5)P3 in vitro and in vivo, negatively regulating intracellular PIP3 levels and PKB/AKT phosphorylation/activity; loss of PTEN in mouse embryonic fibroblasts leads to constitutively elevated AKT activity and resistance to apoptosis. In vitro phosphatase assay, PTEN knockout cells, exogenous PTEN re-expression, PKB/AKT kinase assays Cell High 9778245
1998 Insulin but not muscle contraction activates AKT/PKB in skeletal muscle; insulin-stimulated AKT activity and Ser473 phosphorylation are completely blocked by wortmannin, placing AKT downstream of PI3K specifically in the insulin signaling branch. Immune complex kinase assay, wortmannin inhibition, isolated rat muscle preparations The Journal of biological chemistry High 9614064
1998 SHIP, an inositol 5'-phosphatase recruited via FcγRIIB1 ITIM, inhibits AKT/PKB activation in B cells by depleting PIP3 (converting it to PI-3,4-P2), demonstrating that PIP3 (not PI-3,4-P2) is the dominant in vivo activator of AKT. Co-cross-linking B-cell receptor with FcγRIIB1, SHIP-deficient B cells, FcγRIIB1 ITIM mutants, AKT kinase assay The Journal of biological chemistry High 9852043
1998 AKT phosphorylates and inactivates caspase-9 at Ser196 in vitro and in cells; caspase-9 S196A mutant is resistant to AKT-mediated inhibition and confers AKT-resistant apoptosis, defining a direct anti-apoptotic mechanism. In vitro kinase assay with recombinant caspase-9, S196A mutagenesis, cytosolic extract processing assay, cell death assays Science High 9812896
1999 AKT phosphorylates the Forkhead transcription factor FKHRL1, causing its association with 14-3-3 proteins and cytoplasmic retention; withdrawal of survival factors leads to FKHRL1 dephosphorylation, nuclear translocation, and induction of pro-apoptotic genes including Fas ligand. In vivo phosphorylation, 14-3-3 co-immunoprecipitation, nuclear fractionation, reporter assays, dominant-negative/active AKT Cell High 10102273
1999 AKT directly phosphorylates eNOS at Ser1177 (Ser1179 in bovine), activating NO production in a Ca2+-independent manner; the Ser1177A eNOS mutant is resistant to AKT-mediated activation and shear-stress-induced phosphorylation. In vitro kinase assay, Ser1177A/Ser1179A mutagenesis, adenoviral overexpression of active/inactive AKT, NO measurement Nature High 10376602 10376603
1999 AKT is required for TNF-mediated NF-κB activation: AKT phosphorylates IKKα at Thr23, and mutation of this site blocks NF-κB activation; dominant-negative Akt or PI3K inhibitors suppress TNF-induced NF-κB, while constitutively active AKT induces it. Dominant-negative and constitutively active AKT expression, wortmannin/dominant-negative PI3K, in vitro IKKα phosphorylation, Thr23Ala mutant Nature High 10485710
1999 AKT/PKB associates with IKK upon PDGF stimulation and induces IKK activation leading to NF-κB activation; Ras/PI3K/Akt/IKK/NF-κB constitutes an anti-apoptotic pathway downstream of PDGF. Co-immunoprecipitation of AKT with IKK, dominant-negative constructs, NF-κB reporter assays Nature High 10485711
1999 AKT overexpression induces NF-κB in Jurkat T cells via IκB degradation; this requires both the kinase activity and PH domain of AKT; AKT cooperates with other pathways to activate cytokine promoters. Overexpression of wild-type, kinase-dead, and PH-domain mutant AKT; NF-κB reporter assays; IκB degradation analysis Current biology Medium 10359702
1999 TRANCE activates AKT/PKB through a signaling complex containing TRAF6 and c-Src; c-Src deficiency or Src kinase inhibitors block TRANCE-mediated AKT activation; TRAF6 enhances c-Src kinase activity. Co-immunoprecipitation, c-Src knockout osteoclasts, kinase inhibitors, kinase activity assays Molecular cell High 10635328
2000 Caspases cleave and inactivate AKT/PKB during apoptosis at three sites (including between PH and kinase domains and in C-terminal regulatory domain), generating 40- and 44-kDa fragments with reduced kinase activity; overexpression of a deleted AKT fragment increases apoptotic sensitivity. In vitro caspase cleavage assay, kinase activity measurements, overexpression of truncation fragments Journal of cellular physiology Medium 10623893
2000 C2-ceramide inhibits PKB/AKT1 by activating ceramide-activated protein phosphatase (CAPP) that dephosphorylates AKT1 at Thr308 and Ser473; membrane-anchored (myristoylated) AKT1 is more resistant to ceramide-induced dephosphorylation and apoptosis. In vitro dephosphorylation assay with CAPP, myristoylated-AKT1 expression, phospho-specific immunoblotting, cell death assays in PC12 cells Molecular and cellular neurosciences Medium 10673324
2000 AKT/PKB translocates to the nucleus in response to IGF-I and PDGF in osteoblast-like MC3T3-E1 cells; nuclear translocation is blocked by the PI3K inhibitor LY294002 and correlates with nuclear kinase activity, suggesting a role in proliferative signaling. Subcellular fractionation with Western blot, immune complex kinase assay, confocal microscopy, PI3K inhibitor treatment FEBS letters Medium 10899305
2001 AKT phosphorylates MDM2 at Ser166 and Ser186, promoting its translocation from cytoplasm to nucleus; nuclear MDM2 decreases p53 protein levels and transcriptional activity; PI3K/AKT blockade prevents nuclear entry of MDM2 and increases p53 activity. In vivo phosphorylation mapping, dominant-negative/constitutively active AKT and PI3K constructs, MDM2 localization by fractionation, p53 reporter assays, Ser166/186Ala mutant MDM2 Proceedings of the National Academy of Sciences of the United States of America High 11504915
2001 Constitutively active AKT/PKB induces synthesis of laminin-1 and collagen IV isotypes and promotes their translocation to the basement membrane; dominant-negative AKT inhibits transcription of laminin β1 and collagen IVα1 via promoter-reporter assays. Constitutively active and dominant-negative AKT transfection, promoter-reporter constructs, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America Medium 11734644
2001 Tyrosine phosphorylation by Src-family kinases is required for AKT activation by growth factors; two tyrosine residues near the activation loop are critical, and their YF mutation abolishes AKT kinase activity; c-Src restores AKT activity in SYF cells lacking Src/Yes/Fyn. SYF knockout cells, c-Src reconstitution, Y→F mutagenesis of AKT, kinase activity assays, PP2 inhibitor The Journal of biological chemistry High 11445557
2002 AKT/PKB phosphorylates p27 at Thr157 within its nuclear localization signal, impairing nuclear import; cells with constitutively active AKT mislocalize wild-type p27 to cytoplasm, but p27T157A remains nuclear; cytoplasmic p27 correlates with AKT activation in human breast cancers. In vitro nuclear import assay, Thr157Ala mutagenesis, constitutively active AKT(T308DS473D) transfection, subcellular fractionation, immunofluorescence, tumor samples Nature medicine High 12244302
2002 AKT directly phosphorylates TSC2 (tuberin); phosphorylation destabilizes TSC2 and disrupts its interaction with TSC1, releasing inhibition of mTOR/S6K signaling; AKT-phosphorylated sites T1462 and S939 are constitutively phosphorylated in PTEN-null tumor cells. In vitro kinase assay with recombinant proteins, phospho-site mapping, TSC1/TSC2 co-immunoprecipitation, S6K activity assay Nature cell biology High 12172553
2002 Tuberin (TSC2) is identified by bioinformatics and confirmed as an AKT substrate; AKT phosphorylates tuberin at S939 and T1462 in vitro and in vivo; a tuberin mutant lacking these sites blocks S6K1 activation, placing AKT→TSC2→mTOR→S6K1 in sequence. Bioinformatics-guided substrate identification, in vitro kinase assay, in vivo phosphorylation, dominant-negative tuberin mutant, S6K1 activity Molecular cell High 12150915
2004 ATM directly mediates full AKT activation at Ser473 in response to insulin or ionizing radiation; ATM's PI3K-like domain is responsible; ATM inhibition or siRNA knockdown nearly abolishes Ser473 phosphorylation, and ATM-deficient cells show impaired Forkhead regulation after insulin/radiation. ATM inhibitors, siRNA knockdown, ATM-null (AT patient) cell lines, ATM knockout mice, transfection in COS cells, phospho-Ser473 immunoblotting The Journal of biological chemistry Medium 15546863
2005 The rictor-mTOR complex (mTORC2) directly phosphorylates AKT/PKB on Ser473 in vitro and facilitates subsequent Thr308 phosphorylation by PDK1; RNAi knockdown of rictor or mTOR prevents Ser473 phosphorylation in Drosophila and human cells. In vitro kinase assay with purified mTORC2, rictor RNAi in Drosophila and human cells, phospho-Ser473 immunoblotting, AKT effector activity Science High 15718470
2005 PKB/AKT activates SREBP-1 (but not SREBP-2) nuclear accumulation and drives transcription of fatty acid and cholesterol biosynthesis enzymes including fatty acid synthase (FAS); SREBP activation is required for AKT-induced FAS promoter activity; AKT increases cellular fatty acids and phosphoglycerides. DNA microarray after AKT activation, FAS promoter-reporter, Western blot for nuclear SREBP, lipid quantification by NMR Oncogene Medium 16007182
2006 Prolonged rapamycin treatment disrupts mTORC2 assembly in many cell types, reducing Akt/PKB Ser473 phosphorylation below levels needed for signaling; the pro-apoptotic/antitumor effects of rapamycin are suppressed by a rapamycin-resistant AKT mutant. mTORC2 complex assembly analysis, rapamycin treatment in multiple cell lines, phospho-Ser473 immunoblotting, rapamycin-resistant AKT mutant rescue Molecular cell High 16603397
2006 mSin1 is an essential component of mTORC2 required for its assembly and its ability to phosphorylate AKT/PKB; three mSin1 isoforms create distinct mTORC2 complexes, all capable of phosphorylating AKT in vitro, but only two respond to insulin. mSin1 identification by MS, mSin1 RNAi, in vitro kinase assay, complex assembly analysis Current biology High 16919458
2006 SIN1/MIP1 is an essential mTORC2 subunit required for AKT Ser473 phosphorylation; sin1 genetic ablation eliminates Ser473 phosphorylation and disrupts rictor-mTOR interaction; loss of Ser473 phosphorylation selectively impairs AKT-mediated FoxO1/3a phosphorylation but not TSC2, GSK3, S6K or 4E-BP1. Sin1 knockout cells, rictor-mTOR co-IP, phospho-immunoblotting of multiple AKT substrates Cell High 16962653
2007 PRAS40 binds the mTOR kinase domain and inhibits mTOR activity; AKT phosphorylates PRAS40, causing association with 14-3-3 and relieving mTOR inhibition; this constitutes a mechanism by which insulin/AKT activates mTORC1 independently of (or in addition to) TSC2 phosphorylation. PRAS40-mTOR co-IP, in vitro kinase assay, PRAS40 siRNA, 14-3-3 binding assay, mTOR activity assay Nature cell biology High 17277771
2007 PRAS40 is a raptor-interacting inhibitor of mTORC1; insulin activates AKT-mediated phosphorylation of PRAS40, preventing its inhibition of mTORC1 in cells and in vitro; Rheb-GTP and PRAS40 represent two converging inputs to mTORC1. Raptor co-IP, in vitro mTORC1 kinase assay, AKT phosphorylation of PRAS40 in vitro and in vivo, cell growth assays Molecular cell High 17386266
2007 The AKT1 E17K somatic mutation in the PH domain activates AKT1 by pathological localization to the plasma membrane independent of PIP3; Lys17 forms new hydrogen bonds with phosphoinositide ligand; E17K-AKT1 transforms cells and induces leukemia in mice; E17K decreases sensitivity to allosteric AKT inhibitors. Structural modeling, plasma membrane localization assay, cell transformation assay, mouse leukemia model, allosteric inhibitor sensitivity Nature High 17611497
2008 Plasma membrane raft nanodomains (sphingolipid- and cholesterol-dependent) facilitate AKT recruitment to the membrane upon PIP3 accumulation; disruption of raft formation by inhibiting sphingolipid or cholesterol biosynthesis impairs AKT plasma membrane recruitment and activation. Fluorescence correlation spectroscopy (FCS) in live cells, sphingolipid/cholesterol biosynthesis inhibition, AKT activation readouts Nature chemical biology Medium 18641634
2008 AKT phosphorylates Girdin (an actin-binding protein) and this phosphorylation is required for VEGF-dependent endothelial cell migration; Girdin knockout mice exhibit impaired postnatal retinal vessel remodeling and aortic ring angiogenesis; AKT/Girdin defines a specific pathway in VEGF-mediated angiogenesis. In vitro kinase assay, Girdin siRNA, Girdin knockout mice, endothelial tube formation, in vivo Matrigel angiogenesis assay Nature cell biology High 18264090
2009 AKT directly phosphorylates Skp2 at Ser72, triggering SCF complex formation, E3 ligase activity, and 14-3-3β-dependent cytosolic relocalization of Skp2; phosphorylation-defective Skp2 fails to promote cell proliferation, tumorigenesis, or cell migration; cytosolic Skp2 promotes cell migration in an AKT-dependent manner. In vitro kinase assay, S72A mutagenesis, Co-IP of 14-3-3β, subcellular fractionation, tumor xenograft, migration assay, human cancer correlation Nature cell biology High 19270694
2009 The PH domain of AKT interacts with the kinase domain in the inactive conformation, preventing activation-loop phosphorylation by PDK1; the allosteric inhibitor AKT inhibitor VIII stabilizes this inactive PH-kinase domain interaction with isoform selectivity; FRET/FLIM confirms closed conformation in cells. FRET/two-photon FLIM in living cells, molecular modeling, biochemical assays, allosteric inhibitor profiling PLoS biology High 19166270
2009 DNA-PK can phosphorylate AKT at Ser473 and activate it; together with mTORC2, PIKK family members (DNA-PK and mTORC2) represent stimulus- and context-dependent Ser473 kinases for AKT. Review synthesizing experimental evidence; foundational experiments cited include DNA-PK in vitro kinase assays Current opinion in cell biology Medium 19303758
2010 AKT/PKB phosphorylates Twist-1 at Ser42, and this phosphorylation suppresses p53 upregulation and activation of p53 target genes (p21, Bax) after DNA damage; Twist-1 S42A mutant does not confer resistance to DNA damage-induced apoptosis. In vitro kinase assay, S42A mutagenesis, gamma-irradiation and adriamycin treatment, p53 target gene expression, cell-cycle and apoptosis assays, in vivo phospho-Twist-1 in human cancers Oncogene Medium 20400976
2010 Ack1 (TNK2), a non-receptor tyrosine kinase activated by RTKs, directly phosphorylates AKT at the conserved Tyr176 in the kinase domain; pTyr176-AKT localizes to the plasma membrane and promotes Thr308/Ser473 phosphorylation; activated Ack1 in mouse prostate induces AKT Tyr176 phosphorylation and prostatic intraepithelial neoplasia. In vitro kinase assay, phospho-Tyr176 antibody, Ack1 transgenic mouse, mass spectrometry, Y176F mutagenesis PloS one Medium 20333297
2011 TBK1 directly phosphorylates AKT at both the activation loop (Thr308 equivalent) and hydrophobic motif (Ser473) independently of PDK1 and mTORC2; upon mitogen stimulation or innate immune activation, TBK1 is recruited to the exocyst where it activates AKT; pharmacological TBK1 inhibition selectively impairs exocyst-dependent AKT activation. In vitro kinase assay with TBK1, phospho-site mapping, TBK1 knockout cells, exocyst co-IP, selective TBK1 inhibitor characterization Molecular cell High 21329883
2011 IPMK (inositol polyphosphate multikinase) functions as a PI3-kinase that generates PIP3 downstream of p110 PI3-kinases to activate AKT; IPMK deletion selectively reduces growth-factor-elicited AKT signaling; IPMK acts as a molecular switch — its PI3-kinase activity stimulates AKT while its inositol phosphate kinase activity inhibits it. IPMK knockout cells, PI3-kinase activity assay, wortmannin inhibition, AKT phosphorylation readout, lipid kinase reconstitution Proceedings of the National Academy of Sciences of the United States of America Medium 21220345
2009 AKT binds directly to actin via its N-terminal PH domain; PDGF stimulation increases actin-bound AKT and requires AKT phosphorylation at Thr308/Ser473; phosphorylation-deficient AKT(S473A/T308A) cannot bind actin upon growth factor stimulation; Rac1 and Cdc42 facilitate actin binding. Immunoprecipitation, subcellular fractionation, in vitro binding with recombinant proteins, overlay assay, PH-domain mutants Cellular and molecular life sciences Medium 14685694
2007 AKT1 phosphorylates FoxO3a to prevent its nuclear localization in osteoblasts, suppressing transactivation of the pro-apoptotic gene Bim; disruption of Akt1 in mice leads to increased osteoblast apoptosis via the Akt1/FoxO3a/Bim axis and low-turnover osteopenia. Akt1 knockout mice, ex vivo osteoblast culture, FoxO3a nuclear fractionation, Bim expression analysis, apoptosis assays PloS one High 17957242
2007 AKT1 kinase network controls intracellular survival of Salmonella typhimurium and Mycobacterium tuberculosis; S. typhimurium effector SopB activates AKT1 to control actin dynamics through PAK4 and phagosome-lysosome fusion through AS160-RAB14 pathway; AKT1 inhibitors prevent intracellular bacterial growth. RNAi kinome screen, automated microscopy, AKT1 inhibitors, bacterial growth assays, pathway analysis Nature Medium 18046412
2009 Pin1 (peptidyl-prolyl cis/trans isomerase) interacts with phosphorylated Thr-Pro motifs on AKT and regulates AKT stability and Ser473 phosphorylation; Pin1 knockout or siRNA knockdown compromises AKT stability. Pin1 knockout and siRNA, co-immunoprecipitation, phospho-S473 immunoblotting, stability assays Oncogene Medium 19448664
2011 CK2 phosphorylates AKT at Ser129, hyperactivating AKT; CK2-mediated AKT hyperactivation is required for AKT-dependent phosphorylation of β-catenin at Ser552 and nuclear localization of β-catenin, survivin expression, and cell viability; AKT-S129A mutant reverses CK2-induced β-catenin transcriptional activity. CK2α overexpression, dominant-negative and AKT-S129A mutant co-expression, β-catenin reporter assay, nuclear fractionation, survivin expression, cell viability Journal of cellular physiology Medium 21506126
2011 PKB/AKT phosphorylates TopBP1, inducing TopBP1 oligomerization through its 7th and 8th BRCT domains; Akt-dependent oligomerization is required for TopBP1 to interact with and repress E2F1 pro-apoptotic activity; the same phosphorylation controls TopBP1 interactions with Miz1 and HPV16 E2. In vitro kinase assay, co-immunoprecipitation, oligomerization assay, E2F1 apoptosis reporter, BRCT domain mutants The EMBO journal Medium 17006541
2004 PAK1 (p21-activated kinase-1) can directly phosphorylate AKT at Ser473 in vitro and functions as a PDK2 in cardiomyocytes; PAK1 overexpression induces AKT phosphorylation at Ser473 and Thr308; PAK1 silencing diminishes AKT phosphorylation in vitro and in vivo. In vitro kinase assay with purified PAK1, PAK1 overexpression and silencing in cardiomyocytes, in vivo phospho-AKT analysis Journal of molecular and cellular cardiology Medium 18054038
2004 In C. elegans, akt-1 and akt-2 negatively regulate DNA-damage-induced apoptosis in the germline; akt-1's anti-apoptotic activity is independent of its target daf-16 but dependent on cep-1/p53; AKT-1 suppresses apoptosis but not cell-cycle arrest downstream of the HUS-1/MRT-2 DNA damage checkpoint. C. elegans akt-1/akt-2 mutants, epistasis analysis with daf-16 and cep-1 mutants, germline apoptosis quantification Current biology Medium 17276923
2020 Site-specific phosphorylation of AKT1 at Thr308 and Ser473 differentially controls substrate selectivity; Ser473 phosphorylation can positively or negatively regulate kinase activity in a substrate-dependent fashion; defined phospho-AKT1 variants show both common and distinct substrate preferences revealed by OPAL peptide libraries. Programmed site-specific phosphorylation of AKT1, oriented peptide array libraries (~10^11 peptides), 84-substrate peptide library, bioinformatics discrimination of AKT1 substrates The Journal of biological chemistry High 32350110
2014 The SARS-CoV membrane protein C-terminus interacts with the PH domain of PDK1, disrupting the PDK1-AKT association and reducing AKT activity; this leads to decreased FKHRL1 phosphorylation and activation of caspases 8 and 9. Co-immunoprecipitation of M-protein with PDK1 PH domain, AKT kinase assay, caspase activity assays, FKHRL1 phosphorylation The Biochemical journal Medium 25271362

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science (New York, N.Y.) 5524 15718470
1999 Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 5502 10102273
2007 AKT/PKB signaling: navigating downstream. Cell 4989 17604717
1995 Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 4366 8524413
1999 Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 2980 10376603
2017 AKT/PKB Signaling: Navigating the Network. Cell 2888 28431241
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
1998 Regulation of cell death protease caspase-9 by phosphorylation. Science (New York, N.Y.) 2616 9812896
2002 TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nature cell biology 2517 12172553
1996 Mechanism of activation of protein kinase B by insulin and IGF-1. The EMBO journal 2494 8978681
2013 Discovery and refinement of loci associated with lipid levels. Nature genetics 2409 24097068
2006 Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Molecular cell 2215 16603397
1999 Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 2197 10376602
1998 Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 2129 9778245
1999 NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 1889 10485710
1995 The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 1816 7774014
1997 Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science (New York, N.Y.) 1808 9381178
1999 NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 1608 10485711
1999 Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. The Journal of biological chemistry 1515 10196138
2000 ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Molecular cell 1503 11163209
2004 Rho and Rac take center stage. Cell 1491 14744429
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1997 Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science (New York, N.Y.) 1315 9005852
2002 Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Molecular cell 1296 12150915
2000 The PI3K-PDK1 connection: more than just a road to PKB. The Biochemical journal 1196 10698680
2008 Identification of host proteins required for HIV infection through a functional genomic screen. Science (New York, N.Y.) 1165 18187620
2006 SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 1161 16962653
1996 Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. The Journal of biological chemistry 1090 8940145
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2019 Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature 1039 30842662
2007 A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 1034 17611497
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2007 PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Molecular cell 1006 17386266
2003 Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Current biology : CB 983 12906785
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2001 A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proceedings of the National Academy of Sciences of the United States of America 964 11504915
2007 Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nature cell biology 945 17277771
2012 PI3K-PKB/Akt pathway. Cold Spring Harbor perspectives in biology 859 22952397
2002 PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nature medicine 784 12244302
1999 Induction of NF-kappaB by the Akt/PKB kinase. Current biology : CB 726 10359702
2011 Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skeletal muscle 620 21798082
2004 Structure, regulation and function of PKB/AKT--a major therapeutic target. Biochimica et biophysica acta 579 15023346
2006 mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Current biology : CB 552 16919458
1999 TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Molecular cell 502 10635328
2002 PKB binding proteins. Getting in on the Akt. Cell 470 12419241
2005 The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene 433 16288295
2005 PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene 361 16007182
2003 Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty. Journal of leukocyte biology 354 12773501
2002 Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. British journal of cancer 347 11870534
2005 Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorganic & medicinal chemistry letters 330 15664853
2009 Rac1 GTPase: a "Rac" of all trades. Cellular and molecular life sciences : CMLS 295 19151919
1996 Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. The Biochemical journal 284 8645147
1998 Dissociation of cytokine-induced phosphorylation of Bad and activation of PKB/akt: involvement of MEK upstream of Bad phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 270 9636168
2007 Physiological roles of PKB/Akt isoforms in development and disease. Biochemical Society transactions 262 17371246
2007 Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1. Nature 259 18046412
2017 AKT Inhibition in Solid Tumors With AKT1 Mutations. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 252 28489509
2006 Akt1 in endothelial cell and angiogenesis. Cell cycle (Georgetown, Tex.) 246 16552185
2008 Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nature chemical biology 239 18641634
2013 PKB/Akt-dependent regulation of cell motility. Journal of the National Cancer Institute 233 23355761
2010 The PKB/AKT pathway in cancer. Current pharmaceutical design 231 20214616
2004 Activation of Akt-1 (PKB-alpha) can accelerate ErbB-2-mediated mammary tumorigenesis but suppresses tumor invasion. Cancer research 226 15126356
2007 Akt1 in osteoblasts and osteoclasts controls bone remodeling. PloS one 224 17957242
1999 Regulation of Akt/PKB activity, cellular growth, and apoptosis in prostate carcinoma cells by MMAC/PTEN. Cancer research 223 10363971
2004 Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM. The Journal of biological chemistry 221 15546863
2009 Role of a novel PH-kinase domain interface in PKB/Akt regulation: structural mechanism for allosteric inhibition. PLoS biology 215 19166270
2009 Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB. Nature cell biology 214 19270694
2001 Regulation of Akt/PKB activation by tyrosine phosphorylation. The Journal of biological chemistry 208 11445557
2008 Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin. Nature cell biology 193 18264090
2011 TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation. Molecular cell 191 21329883
2009 PIKKing on PKB: regulation of PKB activity by phosphorylation. Current opinion in cell biology 188 19303758
2001 Wortmannin inhibits pkb/akt phosphorylation and promotes gemcitabine antitumor activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clinical cancer research : an official journal of the American Association for Cancer Research 179 11595724
2000 Inhibition of PKB/Akt1 by C2-ceramide involves activation of ceramide-activated protein phosphatase in PC12 cells. Molecular and cellular neurosciences 174 10673324
1998 The inositol phosphatase SHIP inhibits Akt/PKB activation in B cells. The Journal of biological chemistry 167 9852043
2005 AKT/PKB signaling mechanisms in cancer and chemoresistance. Frontiers in bioscience : a journal and virtual library 166 15569636
2015 Akt/PKB: one kinase, many modifications. The Biochemical journal 151 25997832
2005 Tumor cell sensitization to apoptotic stimuli by selective inhibition of specific Akt/PKB family members. Molecular cancer therapeutics 148 15713898
2005 Regulation of Akt/PKB Ser473 phosphorylation. Molecular cell 148 15837416
2003 Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. Diabetes 144 12663464
2010 Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation. PloS one 137 20333297
2006 The antiproliferative effect of Quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway. Anticancer research 126 16619521
1999 Mutant presenilin-1 induces apoptosis and downregulates Akt/PKB. The Journal of neuroscience : the official journal of the Society for Neuroscience 126 10377346
1998 Insulin, but not contraction, activates Akt/PKB in isolated rat skeletal muscle. The Journal of biological chemistry 123 9614064
1998 A novel integrin-activated pathway forms PKB/Akt-stimulatory phosphatidylinositol 3,4-bisphosphate via phosphatidylinositol 3-phosphate in platelets. The Journal of biological chemistry 113 9417038
2004 Increased constitutive activity of PKB/Akt in tamoxifen resistant breast cancer MCF-7 cells. Breast cancer research and treatment 109 15377841
2003 Increase of AKT/PKB expression correlates with gleason pattern in human prostate cancer. International journal of cancer 106 14520710
2002 Activation of the PKB/AKT pathway by ICAM-2. Immunity 106 11825565
2010 PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage. Oncogene 104 20400976
2011 Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB. Proceedings of the National Academy of Sciences of the United States of America 102 21220345
2000 Cleavage and inactivation of antiapoptotic Akt/PKB by caspases during apoptosis. Journal of cellular physiology 96 10623893
2000 Translocation of Akt/PKB to the nucleus of osteoblast-like MC3T3-E1 cells exposed to proliferative growth factors. FEBS letters 96 10899305
2008 Targeting of PKCzeta and PKB to caveolin-enriched microdomains represents a crucial step underpinning the disruption in PKB-directed signalling by ceramide. The Biochemical journal 94 17983354
2008 Decrease in Akt/PKB signalling in human skeletal muscle by resistance exercise. European journal of applied physiology 94 18535836
2017 PKB/Akt-dependent regulation of inflammation in cancer. Seminars in cancer biology 89 28476657
2005 Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth. Oncogene 87 15782140
2006 Regulation of TopBP1 oligomerization by Akt/PKB for cell survival. The EMBO journal 86 17006541
2007 Creatine enhances differentiation of myogenic C2C12 cells by activating both p38 and Akt/PKB pathways. American journal of physiology. Cell physiology 85 17652429
2009 Peptidyl-prolyl cis/trans isomerase Pin1 is critical for the regulation of PKB/Akt stability and activation phosphorylation. Oncogene 80 19448664
2003 Involvement of the Akt/PKB signaling pathway with disease processes. Molecular and cellular biochemistry 80 14619975
2000 A novel Akt/PKB-related kinase is essential for morphogenesis in Dictyostelium. Current biology : CB 79 10873800
2004 Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle. American journal of physiology. Endocrinology and metabolism 77 15536206
2015 Integrated Akt/PKB signaling in immunomodulation and its potential role in cancer immunotherapy. Journal of the National Cancer Institute 75 26071042
2001 RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation. The EMBO journal 75 11500376
2007 A structural comparison of inhibitor binding to PKB, PKA and PKA-PKB chimera. Journal of molecular biology 74 17275837
2007 Regulation of Akt/PKB activity by P21-activated kinase in cardiomyocytes. Journal of molecular and cellular cardiology 73 18054038
2005 Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading. American journal of physiology. Regulatory, integrative and comparative physiology 73 15821284
2006 Inhibition of LINE-1 expression in the heart decreases ischemic damage by activation of Akt/PKB signaling. Physiological genomics 72 16418318
2001 Inhibition of mammary epithelial apoptosis and sustained phosphorylation of Akt/PKB in MMTV-IGF-II transgenic mice. Cell death and differentiation 72 11313699
2010 PKB/Akt promotes DSB repair in cancer cells through upregulating Mre11 expression following ionizing radiation. Oncogene 71 20956948
2003 Targeting of the Akt/PKB kinase to the actin skeleton. Cellular and molecular life sciences : CMLS 70 14685694
2011 Involvement of Akt-1 and mTOR in sensitivity of breast cancer to targeted therapy. Oncotarget 69 21730367
2008 Neuronal AKAP150 coordinates PKA and Epac-mediated PKB/Akt phosphorylation. Cellular signalling 68 18565730
2004 Inhibition of Chk1 by activated PKB/Akt. Cell cycle (Georgetown, Tex.) 64 15107605
2011 Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of β-catenin transcriptional activity. Journal of cellular physiology 63 21506126
2020 circRNA-AKT1 Sequesters miR-942-5p to Upregulate AKT1 and Promote Cervical Cancer Progression. Molecular therapy. Nucleic acids 62 32193155
2009 Statins inhibit Akt/PKB signaling via P2X7 receptor in pancreatic cancer cells. Biochemical pharmacology 62 19540829
2011 Promiscuous affairs of PKB/AKT isoforms in metabolism. Archives of physiology and biochemistry 59 21214427
2020 Targeting AKT/PKB to improve treatment outcomes for solid tumors. Mutation research 58 32120136
2005 Lithium-mediated downregulation of PKB/Akt and cyclin E with growth inhibition in hepatocellular carcinoma cells. International journal of cancer 57 15723355
2011 Loss of Akt activity increases circulating soluble endoglin release in preeclampsia: identification of inter-dependency between Akt-1 and heme oxygenase-1. European heart journal 56 21411816
2001 Akt/PKB regulates laminin and collagen IV isotypes of the basement membrane. Proceedings of the National Academy of Sciences of the United States of America 56 11734644
2007 AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans. Current biology : CB 54 17276923
2005 Contribution of the PI3K/Akt/PKB signal pathway to maintenance of self-renewal in human embryonic stem cells. FEBS letters 53 15642372
1994 Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds. The American journal of clinical nutrition 53 8074072
2006 Failure to support a genetic contribution of AKT1 polymorphisms and altered AKT signaling in schizophrenia. Journal of neurochemistry 52 16987250
2013 The AKT inhibitor MK-2206 is cytotoxic in hepatocarcinoma cells displaying hyperphosphorylated AKT-1 and synergizes with conventional chemotherapy. Oncotarget 51 24036604
2001 The Akt/PKB pathway is constitutively activated in Theileria-transformed leucocytes, but does not directly control constitutive NF-kappaB activation. Cellular microbiology 50 11488815
2001 Normal Akt/PKB with reduced PI3K activation in insulin-resistant mice. American journal of physiology. Endocrinology and metabolism 50 11701440
2000 Forkhead transcription factors are targets of signalling by the proto-oncogene PKB (C-AKT). Journal of anatomy 50 11197530
2020 Phosphorylation-dependent substrate selectivity of protein kinase B (AKT1). The Journal of biological chemistry 48 32350110
2014 The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1-PKB/Akt signalling. The Biochemical journal 46 25271362