KEGG   PATHWAY: ko04151Help
Entry
ko04151                     Pathway                                

Name
PI3K-Akt signaling pathway
Description
The phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell membrane. PIP3 in turn serves as a second messenger that helps to activate Akt. Once active, Akt can control key cellular processes by phosphorylating substrates involved in apoptosis, protein synthesis, metabolism, and cell cycle.
Class
09130 Environmental Information Processing; 09132 Signal transduction
BRITE hierarchy
Pathway map
ko04151  PI3K-Akt signaling pathway
ko04151

Ortholog table
Module
M00676  PI3K-Akt signaling [PATH:ko04151]
Disease
H00505  FGFR3-related short limb skeletal dysplasia
H00520  Type II collagenopathies
H01338  Myosclerosis
H01340  Bethlem myopathy
H01341  Collagen VI myopathy
H01370  SHORT syndrome
H01387  Activated PI3K-delta syndrome (APDS)
H01388  Hyperprolactinemia
H01511  Mast-cell leukemia
H01740  Macrothrombocytopenia
H01778  Ullrich disease
H01909  Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH)
H01910  Infantile myofibromatosis
H01912  Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi
H02037  Laron syndrome
H02039  Kowarski syndrome
H02040  Insulin-like growth factor I deficiency
H02044  Cutaneous and mucosal venous malformation
H02066  Achondrogenesis type II
H02068  Hypochondroplasia
H02069  SADDAN
H02070  Kniest dysplasia
H02071  Czech dysplasia
H02072  Stickler syndrome
Other DBs
BSID: 692979
GO: 0043491
Orthology
K04357  epidermal growth factor
K08774  transforming growth factor, alpha
K09784  epiregulin
K09782  amphiregulin
K18496  fibroblast growth factor 1
K18497  fibroblast growth factor 2
K04358  fibroblast growth factor
K22603  fibroblast growth factor 19
K22429  fibroblast growth factor 21
K22428  fibroblast growth factor 23
K05451  nerve growth factor, alpha
K02582  nerve growth factor, beta
K04355  brain-derived neurotrophic factor
K04356  neurotrophin 3
K12457  neurotrophin 4
K04526  insulin
K05459  insulin-like growth factor 1
K13769  insulin-like growth factor 2
K04359  platelet-derived growth factor subunit A
K17386  platelet-derived growth factor subunit B
K05450  platelet derived growth factor C/D
K05453  macrophage colony-stimulating factor 1
K05461  KIT ligand
K05454  fms-related tyrosine kinase 3 ligand
K05448  vascular endothelial growth factor A
K16858  vascular endothelial growth factor B
K16859  placenta growth factor
K05449  vascular endothelial growth factor C/D
K05460  hepatocyte growth factor
K05465  angiopoietin 1
K05466  angiopoietin 2
K05467  angiopoietin 4
K05462  ephrin-A
K04361  epidermal growth factor receptor [EC:2.7.10.1]
K05083  receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K05084  receptor tyrosine-protein kinase erbB-3 [EC:2.7.10.1]
K05085  receptor tyrosine-protein kinase erbB-4 [EC:2.7.10.1]
K04362  fibroblast growth factor receptor 1 [EC:2.7.10.1]
K05093  fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094  fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095  fibroblast growth factor receptor 4 [EC:2.7.10.1]
K02583  tumor necrosis factor receptor superfamily member 16
K03176  neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]
K04360  neurotrophic tyrosine kinase receptor type 2 [EC:2.7.10.1]
K04527  insulin receptor [EC:2.7.10.1]
K05087  insulin-like growth factor 1 receptor [EC:2.7.10.1]
K04363  platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089  platelet-derived growth factor receptor beta [EC:2.7.10.1]
K05090  macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1]
K05091  proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1]
K05092  fms-related tyrosine kinase 3 [EC:2.7.10.1]
K05096  FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05097  FMS-like tyrosine kinase 4 [EC:2.7.10.1]
K05098  kinase insert domain protein receptor [EC:2.7.10.1]
K05099  proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05121  endothelial-specific receptor tyrosine kinase [EC:2.7.10.1]
K05103  Eph receptor A2 [EC:2.7.10.1]
K04364  growth factor receptor-binding protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K16172  insulin receptor substrate 1
K10159  toll-like receptor 2
K10160  toll-like receptor 4
K04392  Ras-related C3 botulinum toxin substrate 1
K06856  immunoglobulin heavy chain
K05855  spleen tyrosine kinase [EC:2.7.10.2]
K06465  B-lymphocyte antigen CD19
K12230  phosphoinositide 3-kinase adapter protein 1
K05438  growth hormone
K05439  prolactin
K05418  oncostatin M
K05429  interleukin 2
K04736  interleukin 3
K05405  interleukin 6
K05430  interleukin 4
K05431  interleukin 7
K05414  interferon alpha
K05415  interferon beta
K05437  erythropoietin
K05423  granulocyte colony-stimulating factor
K05080  growth hormone receptor
K05081  prolactin receptor
K05057  oncostatin M receptor
K05068  interleukin 2 receptor alpha
K05069  interleukin 2 receptor beta
K05070  interleukin 2 receptor gamma
K04737  interleukin 3 receptor alpha
K05055  interleukin 6 receptor
K05071  interleukin 4 receptor
K05072  interleukin 7 receptor
K05130  interferon receptor 1
K05131  interferon receptor 2
K05079  erythropoietin receptor
K05061  granulocyte colony-stimulating factor receptor
K11217  Janus kinase 1 [EC:2.7.10.2]
K04447  Janus kinase 2 [EC:2.7.10.2]
K11218  Janus kinase 3 [EC:2.7.10.2]
K06236  collagen, type I, alpha
K19719  collagen, type II, alpha
K06237  collagen, type IV, alpha
K06238  collagen, type VI, alpha
K08131  collagen, type IX, alpha
K05637  laminin, alpha 1/2
K06240  laminin, alpha 3/5
K06241  laminin, alpha 4
K05636  laminin, beta 1
K06243  laminin, beta 2
K06244  laminin, beta 3
K06245  laminin, beta 4
K05635  laminin, gamma 1
K06246  laminin, gamma 2
K06247  laminin, gamma 3
K06248  chondroadherin
K06249  reelin [EC:3.4.21.-]
K16857  thrombospondin 1
K04659  thrombospondin 2/3/4/5
K05717  fibronectin 1
K06250  secreted phosphoprotein 1
K06251  vitronectin
K06252  tenascin
K03900  von Willebrand factor
K06253  integrin binding sialoprotein
K06480  integrin alpha 1
K06481  integrin alpha 2
K06476  integrin alpha 2B
K06482  integrin alpha 3
K06483  integrin alpha 4
K06484  integrin alpha 5
K06485  integrin alpha 6
K06583  integrin alpha 7
K06584  integrin alpha 8
K06585  integrin alpha 9
K06586  integrin alpha 10
K06587  integrin alpha 11
K06487  integrin alpha V
K05719  integrin beta 1
K06493  integrin beta 3
K06525  integrin beta 4
K06588  integrin beta 5
K06589  integrin beta 6
K06590  integrin beta 7
K06591  integrin beta 8
K05725  focal adhesion kinase 1 [EC:2.7.10.2]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03914  coagulation factor II (thrombin) receptor
K04129  muscarinic acetylcholine receptor M1
K04130  muscarinic acetylcholine receptor M2
K04289  lysophosphatidic acid receptor 1
K04291  lysophosphatidic acid receptor 2
K04294  lysophosphatidic acid receptor 3
K04275  lysophosphatidic acid receptor 4
K08390  lysophosphatidic acid receptor 5
K04273  lysophosphatidic acid receptor 6
K04536  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538  guanine nucleotide-binding protein subunit beta-4
K04539  guanine nucleotide-binding protein subunit beta-5
K07826  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K21289  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:2.7.1.153]
K21290  phosphoinositide-3-kinase regulatory subunit 5/6
K06276  3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K07298  serine/threonine-protein kinase 11 [EC:2.7.11.1]
K07198  5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.11]
K08270  DNA-damage-inducible transcript 4
K07206  tuberous sclerosis 1
K07207  tuberous sclerosis 2
K07208  Ras homolog enriched in brain
K08266  target of rapamycin complex subunit LST8
K07203  serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07204  regulatory associated protein of mTOR
K07205  eukaryotic translation initiation factor 4E binding protein 1
K03259  translation initiation factor 4E
K04688  ribosomal protein S6 kinase beta [EC:2.7.11.1]
K03258  translation initiation factor 4B
K02991  small subunit ribosomal protein S6e
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K06071  protein kinase N [EC:2.7.11.13]
K13302  serum/glucocorticoid-regulated kinase 1 [EC:2.7.11.1]
K13303  serum/glucocorticoid-regulated kinase 2 [EC:2.7.11.1]
K13304  serum/glucocorticoid-regulated kinase 3 [EC:2.7.11.1]
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K05631  atrophin-1 interacting protein 3 (BAI1-associated protein 1)
K05629  atrophin-1 interacting protein 1
K01110  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.67 3.1.3.48 3.1.3.16]
K16339  acyl-coenzyme A thioesterase THEM4 [EC:3.1.2.2]
K04382  serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K03456  serine/threonine-protein phosphatase 2A regulatory subunit A
K04354  serine/threonine-protein phosphatase 2A regulatory subunit B
K11583  serine/threonine-protein phosphatase 2A regulatory subunit B''
K11584  serine/threonine-protein phosphatase 2A regulatory subunit B'
K04079  molecular chaperone HtpG
K09487  heat shock protein 90kDa beta
K09554  cell division cycle protein 37
K16333  CREB-regulated transcription coactivator 2
K16340  PH domain and leucine-rich repeat-containing protein phosphatase [EC:3.1.3.16]
K10167  T-cell leukemia/lymphoma 1A
K16836  T-cell leukemia/lymphoma 1B
K16837  mature T-cell proliferation-1 type B1
K13242  nitric-oxide synthase, endothelial [EC:1.14.13.39]
K10605  breast cancer type 1 susceptibility protein [EC:2.3.2.27]
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K00693  glycogen synthase [EC:2.4.1.11]
K01596  phosphoenolpyruvate carboxykinase (GTP) [EC:4.1.1.32]
K01084  glucose-6-phosphatase [EC:3.1.3.9]
K04377  Myc proto-oncogene protein
K04503  G1/S-specific cyclin-D1
K06625  cyclin-dependent kinase inhibitor 1A
K06624  cyclin-dependent kinase inhibitor 1B
K02206  cyclin-dependent kinase 2 [EC:2.7.11.22]
K02089  cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  cyclin-dependent kinase 6 [EC:2.7.11.22]
K10151  G1/S-specific cyclin-D2
K10152  G1/S-specific cyclin-D3
K06626  G1/S-specific cyclin-E1
K09408  forkhead box protein O3
K16332  retinoblastoma-like protein 2
K04389  tumor necrosis factor ligand superfamily member 6
K16341  Bcl-2-like protein 11
K16197  14-3-3 protein beta/theta/zeta
K06630  14-3-3 protein epsilon
K16198  14-3-3 protein gamma/eta
K02158  Bcl-2-antagonist of cell death
K04570  Bcl-2-like 1 (apoptosis regulator Bcl-X)
K02161  apoptosis regulator Bcl-2
K04399  caspase 9 [EC:3.4.22.62]
K05870  cyclic AMP-responsive element-binding protein 1
K04450  cyclic AMP-dependent transcription factor ATF-2
K04374  cyclic AMP-dependent transcription factor ATF-4
K09048  cyclic AMP-responsive element-binding protein 3
K09047  cyclic AMP-responsive element-binding protein 5
K09049  cyclic AMP-dependent transcription factor ATF-6 beta
K02539  myeloid leukemia cell differntiation protein MCL-1
K08524  retinoid X receptor alpha
K04465  nuclear receptor subfamily 4 group A member 1
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K04735  transcription factor p65
K02580  nuclear factor NF-kappa-B p105 subunit
K09420  transcriptional activator Myb
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K04451  tumor protein p53
Compound
C00020  AMP
C00533  Nitric oxide
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Engelman JA, Luo J, Cantley LC
  Title
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.
  Journal
Nat Rev Genet 7:606-19 (2006)
DOI:10.1038/nrg1879
Reference
  Authors
Song G, Ouyang G, Bao S
  Title
The activation of Akt/PKB signaling pathway and cell survival.
  Journal
J Cell Mol Med 9:59-71 (2005)
DOI:10.1111/j.1582-4934.2005.tb00337.x
Reference
  Authors
Hers I, Vincent EE, Tavare JM
  Title
Akt signalling in health and disease.
  Journal
Cell Signal 23:1515-27 (2011)
DOI:10.1016/j.cellsig.2011.05.004
Reference
  Authors
Duronio V
  Title
The life of a cell: apoptosis regulation by the PI3K/PKB pathway.
  Journal
Biochem J 415:333-44 (2008)
DOI:10.1042/BJ20081056
Reference
  Authors
Kim D, Chung J.
  Title
Akt: versatile mediator of cell survival and beyond.
  Journal
J Biochem Mol Biol 35:106-15 (2002)
Reference
  Authors
Koyasu S
  Title
The role of PI3K in immune cells.
  Journal
Nat Immunol 4:313-9 (2003)
DOI:10.1038/ni0403-313
Reference
  Authors
Okkenhaug K, Vanhaesebroeck B.
  Title
PI3K in lymphocyte development, differentiation and activation.
  Journal
Nat Rev Immunol 3:317-30 (2003)
DOI:10.1038/nri1056
Reference
  Authors
Richardson CJ, Schalm SS, Blenis J
  Title
PI3-kinase and TOR: PIKTORing cell growth.
  Journal
Semin Cell Dev Biol 15:147-59 (2004)
DOI:10.1016/j.semcdb.2003.12.023
Reference
  Authors
Zhang X, Tang N, Hadden TJ, Rishi AK
  Title
Akt, FoxO and regulation of apoptosis.
  Journal
Biochim Biophys Acta 1813:1978-86 (2011)
DOI:10.1016/j.bbamcr.2011.03.010
Reference
  Authors
Georgescu MM
  Title
PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control.
  Journal
Genes Cancer 1:1170-7 (2010)
DOI:10.1177/1947601911407325
Reference
  Authors
West KA, Castillo SS, Dennis PA
  Title
Activation of the PI3K/Akt pathway and chemotherapeutic resistance.
  Journal
Drug Resist Updat 5:234-48 (2002)
DOI:10.1016/S1368-7646(02)00120-6
Reference
PMID:9838078
  Authors
Wymann MP, Pirola L
  Title
Structure and function of phosphoinositide 3-kinases.
  Journal
Biochim Biophys Acta 1436:127-50 (1998)
DOI:10.1016/S0005-2760(98)00139-8
Reference
  Authors
Moelling K, Schad K, Bosse M, Zimmermann S, Schweneker M
  Title
Regulation of Raf-Akt Cross-talk.
  Journal
J Biol Chem 277:31099-106 (2002)
DOI:10.1074/jbc.M111974200
Reference
  Authors
Kikani CK, Dong LQ, Liu F
  Title
"New"-clear functions of PDK1: beyond a master kinase in the cytosol?
  Journal
J Cell Biochem 96:1157-62 (2005)
DOI:10.1002/jcb.20651
Reference
  Authors
Blume-Jensen P, Hunter T
  Title
Oncogenic kinase signalling.
  Journal
Nature 411:355-65 (2001)
DOI:10.1038/35077225
Reference
  Authors
Osaki M, Oshimura M, Ito H
  Title
PI3K-Akt pathway: its functions and alterations in human cancer.
  Journal
Apoptosis 9:667-76 (2004)
DOI:10.1023/B:APPT.0000045801.15585.dd
Reference
  Authors
Noguchi M, Ropars V, Roumestand C, Suizu F
  Title
Proto-oncogene TCL1: more than just a coactivator for Akt.
  Journal
FASEB J 21:2273-84 (2007)
DOI:10.1096/fj.06-7684com
Reference
  Authors
Lemmon MA, Schlessinger J
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 141:1117-34 (2010)
DOI:10.1016/j.cell.2010.06.011
Reference
  Authors
Skaper SD
  Title
The neurotrophin family of neurotrophic factors: an overview.
  Journal
Methods Mol Biol 846:1-12 (2012)
DOI:10.1007/978-1-61779-536-7_1
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