Entry
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
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Orthology
K04357 epidermal growth factor
K08774 transforming growth factor, alpha
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
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
K05454 fms-related tyrosine kinase 3 ligand
K05448 vascular endothelial growth factor A
K16858 vascular endothelial growth factor B
K05449 vascular endothelial growth factor C/D
K05460 hepatocyte growth factor
K05452 glial cell derived neurotrophic factor
K02583 tumor necrosis factor receptor superfamily member 16
K04364 growth factor receptor-bound protein 2
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K16172 insulin receptor substrate 1
K04392 Ras-related C3 botulinum toxin substrate 1
K06856 immunoglobulin heavy chain
K06465 B-lymphocyte antigen CD19
K12230 phosphoinositide 3-kinase adapter protein 1
K05423 granulocyte colony-stimulating factor
K05080 growth hormone receptor
K05068 interleukin 2 receptor alpha
K05069 interleukin 2 receptor beta
K05070 interleukin 2 receptor gamma
K04737 interleukin 3 receptor alpha
K05079 erythropoietin receptor
K05061 granulocyte colony-stimulating factor receptor
K06250 secreted phosphoprotein 1
K06253 integrin binding sialoprotein
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
K07198 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31 ]
K08270 DNA-damage-inducible transcript 4
K07208 Ras homolog enriched in brain
K08266 target of rapamycin complex subunit LST8
K07204 regulatory associated protein of mTOR
K07205 eukaryotic translation initiation factor 4E binding protein 1
K03259 translation initiation factor 4E
K03258 translation initiation factor 4B
K02991 small subunit ribosomal protein S6e
K05631 atrophin-1 interacting protein 3 (BAI1-associated protein 1)
K05629 atrophin-1 interacting protein 1
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
K04377 Myc proto-oncogene protein
K04503 G1/S-specific cyclin-D1
K06625 cyclin-dependent kinase inhibitor 1A
K06624 cyclin-dependent kinase inhibitor 1B
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
K16197 14-3-3 protein beta/theta/zeta
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
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
Compound
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
Reference
Authors
Song G, Ouyang G, Bao S
Title
The activation of Akt/PKB signaling pathway and cell survival.
Journal
Reference
Authors
Hers I, Vincent EE, Tavare JM
Title
Akt signalling in health and disease.
Journal
Reference
Authors
Duronio V
Title
The life of a cell: apoptosis regulation by the PI3K/PKB pathway.
Journal
Reference
Authors
Kim D, Chung J.
Title
Akt: versatile mediator of cell survival and beyond.
Journal
Reference
Authors
Koyasu S
Title
The role of PI3K in immune cells.
Journal
Reference
Authors
Okkenhaug K, Vanhaesebroeck B.
Title
PI3K in lymphocyte development, differentiation and activation.
Journal
Reference
Authors
Richardson CJ, Schalm SS, Blenis J
Title
PI3-kinase and TOR: PIKTORing cell growth.
Journal
Reference
Authors
Zhang X, Tang N, Hadden TJ, Rishi AK
Title
Akt, FoxO and regulation of apoptosis.
Journal
Reference
Authors
Georgescu MM
Title
PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control.
Journal
Reference
Authors
West KA, Castillo SS, Dennis PA
Title
Activation of the PI3K/Akt pathway and chemotherapeutic resistance.
Journal
Reference
Authors
Wymann MP, Pirola L
Title
Structure and function of phosphoinositide 3-kinases.
Journal
Reference
Authors
Moelling K, Schad K, Bosse M, Zimmermann S, Schweneker M
Title
Regulation of Raf-Akt Cross-talk.
Journal
Reference
Authors
Kikani CK, Dong LQ, Liu F
Title
"New"-clear functions of PDK1: beyond a master kinase in the cytosol?
Journal
Reference
Authors
Blume-Jensen P, Hunter T
Title
Oncogenic kinase signalling.
Journal
Reference
Authors
Osaki M, Oshimura M, Ito H
Title
PI3K-Akt pathway: its functions and alterations in human cancer.
Journal
Reference
Authors
Noguchi M, Ropars V, Roumestand C, Suizu F
Title
Proto-oncogene TCL1: more than just a coactivator for Akt.
Journal
Reference
Authors
Lemmon MA, Schlessinger J
Title
Cell signaling by receptor tyrosine kinases.
Journal
Reference
Authors
Skaper SD
Title
The neurotrophin family of neurotrophic factors: an overview.
Journal
Related pathway
ko00010 Glycolysis / Gluconeogenesis
ko04062 Chemokine signaling pathway
ko04064 NF-kappa B signaling pathway
ko04620 Toll-like receptor signaling pathway
ko04662 B cell receptor signaling pathway
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