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
|
Pathway map |

|
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 |
|
Disease |
H00505 | FGFR3-related short limb skeletal dysplasia |
H00520 | Type II collagenopathies |
H01387 | Activated PI3K-delta syndrome |
H01909 | Hypoinsulinemic hypoglycemia with hemihypertrophy |
H01910 | Infantile myofibromatosis |
H01912 | Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi |
H02040 | Insulin-like growth factor I deficiency |
H02044 | Cutaneous and mucosal venous malformation |
H02066 | Achondrogenesis type II |
H02434 | Diffuse large B-cell lymphoma, not otherwise specified |
|
Drug |
D04262 | Fostriecin sodium (USAN) |
D04696 | Lestaurtinib (USAN/INN) |
D04870 | Mecasermin rinfabate (USAN/INN) |
D05029 | Midostaurin (JAN/USAN/INN) |
D06221 | Triciribine phosphate (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) |
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) |
D10797 | Copanlisib hydrochloride (USAN) |
D10798 | Copanlisib hydrochloride hydrate (JAN) |
D10891 | Capmatinib hydrochloride (USAN) |
D10926 | Entrectinib (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 (USAN) |
D11209 | Entospletinib (USAN/INN) |
D11289 | Rivoceranib mesylate (USAN) |
D11323 | Umbralisib tosylate (USAN) |
D11338 | Loncastuximab tesirine (USAN) |
D11354 | Nemiralisib succinate (USAN) |
D11371 | Capivasertib (JAN/USAN) |
D11461 | Derazantinib hydrochloride (USAN) |
D11486 | Lonapegsomatropin (USAN/INN) |
D11506 | Parsaclisib hydrochloride (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) |
|
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] |
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] |
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 |
|
LinkDB |
|