Entry
Name
PI3K-Akt signaling pathway - Homo sapiens (human)
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
Network
Element
N00030 EGF-EGFR-RAS-PI3K signaling pathway
N00033 EGF-EGFR-PI3K signaling pathway
N00037 FGF-FGFR-PI3K signaling pathway
N00039 PDGF-PDGFR-PI3K signaling pathway
N00043 HGF-MET-PI3K signaling pathway
N00045 KITLG-KIT-PI3K signaling pathway
N00182 IGF-IGFR-PI3K-NFKB signaling pathway
N00218 FLT3LG-FLT3-RAS-PI3K signaling pathway
N00220 PTEN-PIP3-AKT signaling pathway
N00231 TGFA-EGFR-PI3K signaling pathway
N00234 IGF2-IGF1R-PI3K signaling pathway
N00282 EREG-EGFR-PI3K signaling pathway
N00284 AREG-EGFR-PI3K signaling pathway
N00342 MAGI-PTEN signaling pathway
N00355 PP2A-AKT signaling pathway
N00390 EGF-EGFR-PI3K-NFKB signaling pathway
N00582 IGF-IGF1R-PI3K signaling pathway
N01656 GF-RTK-PI3K signaling pathway
N01657 GPCR-PI3K signaling pathway
N01658 GF-RTK-RAS-PI3K signaling pathway
N01695 BCR-BCAP/CD19-PI3K signaling pathway
Drug
D04262 Fostriecin sodium (USAN)
D04696 Lestaurtinib (USAN/INN)
D04870 Mecasermin rinfabate (USAN/INN)
D05029 Midostaurin (JAN/USAN/INN)
D06221 Triciribine phosphate (USAN)
D06402 Sunitinib malate (JAN/USAN)
D06554 Alvespimycin hydrochloride (USAN)
D06889 Pegfilgrastim (USAN/INN)
D08344 Tozasertib lactate (USAN)
D08544 Toceranib phosphate (USAN)
D08878 Brivanib alaninate (JAN/USAN/INN)
D08907 Dovitinib lactate (USAN)
D08947 Motesanib diphosphate (USAN)
D08956 Omacetaxine mepesuccinate (USAN)
D09375 Retaspimycin (USAN/INN)
D09376 Retaspimycin hydrochloride (USAN)
D10095 Cabozantinib s-malate (USAN)
D10190 Tivozanib hydrochloride (USAN)
D10382 Afuresertib hydrochloride (USAN)
D10465 Golvatinib tartrate (USAN)
D10560 Idelalisib (JAN/USAN/INN)
D10609 Buparlisib hydrochloride (JAN/USAN)
D10616 Dactolisib tosylate (USAN)
D10647 Luminespib mesylate (USAN)
D10652 Palbociclib isethionate (USAN)
D10688 Abemaciclib (JAN/USAN/INN)
D10797 Copanlisib hydrochloride (USAN)
D10798 Copanlisib hydrochloride hydrate (JAN)
D10891 Capmatinib hydrochloride (USAN)
D10926 Entrectinib (JAN/USAN/INN)
D10927 Erdafitinib (JAN/USAN/INN)
D10945 Itacitinib adipate (JAN/USAN)
D10979 Ribociclib succinate (USAN)
D11011 Alpelisib (JAN/USAN/INN)
D11073 Tepotinib hydrochloride (USAN)
D11074 Ipatasertib hydrochloride (JAN)
D11126 Navicixizumab (USAN/INN)
D11140 Sitravatinib (USAN/INN)
D11144 Axicabtagene ciloleucel (USAN)
D11159 Leniolisib phosphate (JAN/USAN)
D11188 Eflapegrastim (USAN/INN)
D11209 Entospletinib (USAN/INN)
D11270 Pexidartinib (USAN/INN)
D11271 Pexidartinib hydrochloride (JAN/USAN)
D11289 Rivoceranib mesylate (USAN)
D11323 Umbralisib tosylate (USAN)
D11338 Loncastuximab tesirine (USAN)
D11354 Nemiralisib succinate (USAN)
D11371 Capivasertib (JAN/USAN)
D11417 Pemigatinib (JAN/USAN/INN)
D11461 Derazantinib hydrochloride (USAN)
D11506 Parsaclisib hydrochloride (JAN/USAN)
D11508 Miransertib mesylate (USAN)
D11541 Sitravatinib malate (USAN)
D11600 Zotiraciclib citrate (USAN)
D11658 Duvelisib hydrate (JAN)
D11677 Gusacitinib hydrochloride (USAN)
D11757 Inebilizumab (USAN/INN)
D11766 Onalespib lactate (USAN)
D11773 Tesevatinib tosylate (USAN)
D11880 Brexucabtagene autoleucel (USAN)
D11962 Murizatoclax (USAN/INN)
D11977 Fruquintinib (JAN/USAN)
D11986 Efbemalenograstim alfa (USAN/INN)
D11987 Trilaciclib dihydrochloride
D11990 Lisocabtagene maraleucel (USAN/INN)
D11991 Zenocutuzumab (USAN/INN)
D12009 Zandelisib (JAN/USAN/INN)
D12184 Patritumab deruxtecan (USAN/INN)
D12230 Poziotinib hydrochloride (USAN)
D12308 Pivekimab sunirine (USAN)
D12363 Taletrectinib (USAN/INN)
D12364 Taletrectinib adipate (USAN)
D12386 Melredableukin alfa (USAN/INN)
D12405 Tasurgratinib succinate (JAN)
D12409 Barzolvolimab (USAN/INN)
D12442 Tucatinib ethanolate (JAN)
D12502 Golidocitinib (USAN/INN)
D12526 Catequentinib (USAN/INN)
D12537 Catequentinib hydrochloride (USAN)
D12545 Tinengotinib (USAN/INN)
D12557 Elzovantinib (USAN/INN)
D12575 Povorcitinib (USAN/INN)
D12576 Povorcitinib phosphate (USAN)
D12600 Bezuclastinib (USAN/INN)
D12624 Paridiprubart (USAN/INN)
D12635 Sozinibercept (USAN/INN)
D12640 Divarasib adipate (USAN)
D12642 Fipaxalparant (USAN/INN)
D12650 Zanzalintinib (USAN/INN)
D12651 Zanzalintinib fumarate (USAN)
D12705 Gumarontinib hydrate (JAN)
D12731 Anumigilimab (USAN/INN)
D12809 Bafisontamab (USAN/INN)
D12837 Risovalisib mesilate hydrate (JAN)
D12954 Sovleplenib acetate (USAN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
7039 TGFA; transforming growth factor alpha [KO:K08774 ]
8822 FGF17; fibroblast growth factor 17 [KO:K04358 ]
2255 FGF10; fibroblast growth factor 10 [KO:K04358 ]
8823 FGF16; fibroblast growth factor 16 [KO:K04358 ]
8817 FGF18; fibroblast growth factor 18 [KO:K04358 ]
9965 FGF19; fibroblast growth factor 19 [KO:K22603 ]
8074 FGF23; fibroblast growth factor 23 [KO:K22428 ]
627 BDNF; brain derived neurotrophic factor [KO:K04355 ]
3479 IGF1; insulin like growth factor 1 [KO:K05459 ]
3481 IGF2; insulin like growth factor 2 [KO:K13769 ]
5154 PDGFA; platelet derived growth factor subunit A [KO:K04359 ]
5155 PDGFB; platelet derived growth factor subunit B [KO:K17386 ]
56034 PDGFC; platelet derived growth factor C [KO:K05450 ]
80310 PDGFD; platelet derived growth factor D [KO:K05450 ]
1435 CSF1; colony stimulating factor 1 [KO:K05453 ]
2323 FLT3LG; fms related receptor tyrosine kinase 3 ligand [KO:K05454 ]
7422 VEGFA; vascular endothelial growth factor A [KO:K05448 ]
7423 VEGFB; vascular endothelial growth factor B [KO:K16858 ]
7424 VEGFC; vascular endothelial growth factor C [KO:K05449 ]
2277 VEGFD; vascular endothelial growth factor D [KO:K05449 ]
2668 GDNF; glial cell derived neurotrophic factor [KO:K05452 ]
4804 NGFR; nerve growth factor receptor [KO:K02583 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
3667 IRS1; insulin receptor substrate 1 [KO:K16172 ]
118788 PIK3AP1; phosphoinositide-3-kinase adaptor protein 1 [KO:K12230 ]
1442 CSH1; chorionic somatomammotropin hormone 1 [KO:K05438 ]
1443 CSH2; chorionic somatomammotropin hormone 2 [KO:K05438 ]
1444 CSHL1; chorionic somatomammotropin hormone like 1 [KO:K05438 ]
1440 CSF3; colony stimulating factor 3 [KO:K05423 ]
3559 IL2RA; interleukin 2 receptor subunit alpha [KO:K05068 ]
3560 IL2RB; interleukin 2 receptor subunit beta [KO:K05069 ]
3561 IL2RG; interleukin 2 receptor subunit gamma [KO:K05070 ]
3563 IL3RA; interleukin 3 receptor subunit alpha [KO:K04737 ]
3454 IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130 ]
3455 IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131 ]
1441 CSF3R; colony stimulating factor 3 receptor [KO:K05061 ]
1277 COL1A1; collagen type I alpha 1 chain [KO:K06236 ]
1278 COL1A2; collagen type I alpha 2 chain [KO:K06236 ]
1280 COL2A1; collagen type II alpha 1 chain [KO:K19719 ]
1284 COL4A2; collagen type IV alpha 2 chain [KO:K06237 ]
1286 COL4A4; collagen type IV alpha 4 chain [KO:K06237 ]
1288 COL4A6; collagen type IV alpha 6 chain [KO:K06237 ]
1282 COL4A1; collagen type IV alpha 1 chain [KO:K06237 ]
1287 COL4A5; collagen type IV alpha 5 chain [KO:K06237 ]
1285 COL4A3; collagen type IV alpha 3 chain [KO:K06237 ]
1291 COL6A1; collagen type VI alpha 1 chain [KO:K06238 ]
1292 COL6A2; collagen type VI alpha 2 chain [KO:K06238 ]
1293 COL6A3; collagen type VI alpha 3 chain [KO:K06238 ]
1297 COL9A1; collagen type IX alpha 1 chain [KO:K08131 ]
1298 COL9A2; collagen type IX alpha 2 chain [KO:K08131 ]
1299 COL9A3; collagen type IX alpha 3 chain [KO:K08131 ]
1311 COMP; cartilage oligomeric matrix protein [KO:K04659 ]
3381 IBSP; integrin binding sialoprotein [KO:K06253 ]
3674 ITGA2B; integrin subunit alpha 2b [KO:K06476 ]
8515 ITGA10; integrin subunit alpha 10 [KO:K06586 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
2149 F2R; coagulation factor II thrombin receptor [KO:K03914 ]
1128 CHRM1; cholinergic receptor muscarinic 1 [KO:K04129 ]
1129 CHRM2; cholinergic receptor muscarinic 2 [KO:K04130 ]
1902 LPAR1; lysophosphatidic acid receptor 1 [KO:K04289 ]
9170 LPAR2; lysophosphatidic acid receptor 2 [KO:K04291 ]
23566 LPAR3; lysophosphatidic acid receptor 3 [KO:K04294 ]
2846 LPAR4; lysophosphatidic acid receptor 4 [KO:K04275 ]
57121 LPAR5; lysophosphatidic acid receptor 5 [KO:K08390 ]
10161 LPAR6; lysophosphatidic acid receptor 6 [KO:K04273 ]
2790 GNG10; G protein subunit gamma 10 [KO:K04545 ]
2791 GNG11; G protein subunit gamma 11 [KO:K04546 ]
2792 GNGT1; G protein subunit gamma transducin 1 [KO:K04548 ]
2793 GNGT2; G protein subunit gamma transducin 2 [KO:K04549 ]
5294 PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289 ] [EC:2.7.1.153 ]
23533 PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290 ]
146850 PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290 ]
54541 DDIT4; DNA damage inducible transcript 4 [KO:K08270 ]
6009 RHEB; Ras homolog, mTORC1 binding [KO:K07208 ]
64223 MLST8; MTOR associated protein, LST8 homolog [KO:K08266 ]
57521 RPTOR; regulatory associated protein of MTOR complex 1 [KO:K07204 ]
1978 EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205 ]
1977 EIF4E; eukaryotic translation initiation factor 4E [KO:K03259 ]
9470 EIF4E2; eukaryotic translation initiation factor 4E family member 2 [KO:K03259 ]
253314 EIF4E1B; eukaryotic translation initiation factor 4E family member 1B [KO:K03259 ]
1975 EIF4B; eukaryotic translation initiation factor 4B [KO:K03258 ]
9223 MAGI1; membrane associated guanylate kinase, WW and PDZ domain containing 1 [KO:K05631 ]
9863 MAGI2; membrane associated guanylate kinase, WW and PDZ domain containing 2 [KO:K05629 ]
5519 PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456 ]
5518 PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456 ]
5520 PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354 ]
5521 PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354 ]
5522 PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354 ]
55844 PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354 ]
28227 PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583 ]
55012 PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583 ]
5523 PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583 ]
5526 PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584 ]
5527 PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584 ]
5528 PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584 ]
5529 PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584 ]
5525 PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584 ]
3320 HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079 ]
3326 HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079 ]
7184 HSP90B1; heat shock protein 90 beta family member 1 [KO:K09487 ]
11140 CDC37; cell division cycle 37, HSP90 cochaperone [KO:K09554 ]
200186 CRTC2; CREB regulated transcription coactivator 2 [KO:K16333 ]
23239 PHLPP1; PH domain and leucine rich repeat protein phosphatase 1 [KO:K16340 ] [EC:3.1.3.16 ]
23035 PHLPP2; PH domain and leucine rich repeat protein phosphatase 2 [KO:K16340 ] [EC:3.1.3.16 ]
8115 TCL1A; TCL1 family AKT coactivator A [KO:K10167 ]
9623 TCL1B; TCL1 family AKT coactivator B [KO:K16836 ]
4515 MTCP1; mature T cell proliferation 1 [KO:K16837 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
1027 CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624 ]
5934 RBL2; RB transcriptional corepressor like 2 [KO:K16332 ]
7534 YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197 ]
7529 YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197 ]
10971 YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197 ]
7531 YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630 ]
7533 YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198 ]
7532 YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198 ]
572 BAD; BCL2 associated agonist of cell death [KO:K02158 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
1386 ATF2; activating transcription factor 2 [KO:K04450 ]
468 ATF4; activating transcription factor 4 [KO:K04374 ]
10488 CREB3; cAMP responsive element binding protein 3 [KO:K09048 ]
90993 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
64764 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
84699 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
148327 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
9586 CREB5; cAMP responsive element binding protein 5 [KO:K09047 ]
1388 ATF6B; activating transcription factor 6 beta [KO:K09049 ]
4170 MCL1; MCL1 apoptosis regulator, BCL2 family member [KO:K02539 ]
3164 NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
4602 MYB; MYB proto-oncogene, transcription factor [KO:K09420 ]
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
hsa04620 Toll-like receptor signaling pathway
hsa04662 B cell receptor signaling pathway
KO pathway