KEGG   PATHWAY: pgig04390
Entry
pgig04390                   Pathway                                
Name
Hippo signaling pathway - Pteropus giganteus (Indian flying fox)
Description
Hippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor Salvador and LATS1 and LATS2. In response to high cell densities, activated LATS1/2 phosphorylates the transcriptional coactivators YAP and TAZ, promoting its cytoplasmic localization, leading to cell apoptosis and restricting organ size overgrowth. When the Hippo pathway is inactivated at low cell density, YAP/TAZ translocates into the nucleus to bind to the transcription enhancer factor (TEAD/TEF) family of transcriptional factors to promote cell growth and proliferation. YAP/TAZ also interacts with other transcriptional factors or signaling molecules, by which Hippo pathway-mediated processes are interconnected with those of other key signaling cascades, such as those mediated by TGF-beta and Wnt growth factors.
Class
Environmental Information Processing; Signal transduction
Pathway map
pgig04390  Hippo signaling pathway
pgig04390

Other DBs
GO: 0035329
Organism
Pteropus giganteus (Indian flying fox) [GN:pgig]
Gene
120619316  CRB1; LOW QUALITY PROTEIN: protein crumbs homolog 1 [KO:K16681]
120601619  CRB2; protein crumbs homolog 2 isoform X1 [KO:K16681]
120584128  PARD3; partitioning defective 3 homolog isoform X1 [KO:K04237]
120603813  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
120593945  PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
120583394  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
120614115  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
120604376  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
120621982  PATJ; inaD-like protein isoform X1 [KO:K06092]
120612757  PALS1; MAGUK p55 subfamily member 5 isoform X1 [KO:K06091]
120612313  AMOT; angiomotin isoform X1 [KO:K16819]
120618087  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
120596579  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
120593865  CDH1; cadherin-1 [KO:K05689]
120582260  LIMD1; LIM domain-containing protein 1 isoform X1 [KO:K16682]
120593773  AJUBA; LIM domain-containing protein ajuba isoform X1 [KO:K16682]
120622843  Wilms tumor protein 1-interacting protein isoform X1 [KO:K16682]
120601977  NF2; merlin isoform X1 [KO:K16684]
120614595  WWC1; protein KIBRA isoform X1 [KO:K16685]
120617953  FRMD1; FERM domain-containing protein 1 [KO:K16821]
120604432  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
120604447  SAV1; protein salvador homolog 1 [KO:K16686]
120595596  STK3; serine/threonine-protein kinase 3 isoform X1 [KO:K04412]
120588196  RASSF6; ras association domain-containing protein 6 isoform X1 [KO:K09854]
120582387  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
120581292  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120589049  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120583980  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120621983  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
120581501  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
120613401  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
120582867  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
120602889  LATS2; serine/threonine-protein kinase LATS2 isoform X1 [KO:K08791] [EC:2.7.11.1]
120589373  LATS1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
120594628  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
120588175  MOB1B; MOB kinase activator 1B isoform X1 [KO:K06685]
120616096  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
120584763  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
120621819  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
120619137  TP53BP2; LOW QUALITY PROTEIN: apoptosis-stimulating of p53 protein 2 [KO:K16823]
120600192  LLGL2; LLGL scribble cell polarity complex component 2 isoform X1 [KO:K06094]
120589851  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
120588792  SCRIB; protein scribble homolog isoform X1 [KO:K16175]
120592931  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
120590423  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
120585407  DLG3; LOW QUALITY PROTEIN: disks large homolog 3 [KO:K21098]
120589628  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
120609572  DLG5; disks large homolog 5 isoform X1 [KO:K24050]
120600129  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
120614818  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
120614879  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
120609176  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
120585713  TP73; tumor protein p73 [KO:K10148]
120617900  BBC3; LOW QUALITY PROTEIN: bcl-2-binding component 3 [KO:K10132]
120603218  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
120615577  TEAD2; transcriptional enhancer factor TEF-4 [KO:K09448]
120607324  TEAD4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
120597687  TEAD3; transcriptional enhancer factor TEF-5 isoform X1 [KO:K09448]
120592307  CCN2; CCN family member 2 [KO:K06827]
120606282  GLI2; LOW QUALITY PROTEIN: zinc finger protein GLI2 [KO:K16798]
120587962  AREG; amphiregulin [KO:K09782]
120600298  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
120588192  alpha-fetoprotein [KO:K16144]
120588194  alpha-fetoprotein-like isoform X1 [KO:K16144]
120584403  ITGB2; integrin beta-2 [KO:K06464]
120581479  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
120586591  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
120619172  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
120619522  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
120597204  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
120586804  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
120585683  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
120585764  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120604483  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
120585140  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
120591668  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
120603409  BMP2; bone morphogenetic protein 2 [KO:K21283]
120604412  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
120594850  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
120607668  BMP6; bone morphogenetic protein 6 [KO:K16620]
120603859  BMP7; bone morphogenetic protein 7 [KO:K16621]
120614037  BMP8B; bone morphogenetic protein 8B [KO:K16622]
120593258  BMP8A; bone morphogenetic protein 8A [KO:K16622]
120603326  GDF5; growth/differentiation factor 5 [KO:K04664]
120605465  GDF6; growth/differentiation factor 6 [KO:K20012]
120622114  GDF7; growth/differentiation factor 7 [KO:K20013]
120583729  AMH; muellerian-inhibiting factor [KO:K04665]
120609617  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
120588330  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
120587545  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
120613329  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
120603513  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
120622067  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
120618559  WNT1; proto-oncogene Wnt-1 [KO:K03209]
120585033  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
120601108  WNT2; protein Wnt-2 [KO:K00182]
120616644  WNT3A; protein Wnt-3a [KO:K00312]
120589261  WNT3; proto-oncogene Wnt-3 [KO:K00312]
120596198  WNT4; protein Wnt-4 [KO:K00408]
120606289  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
120607346  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
120587668  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
120602874  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
120613810  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
120581156  WNT8A; protein Wnt-8a isoform X1 [KO:K00714]
120608938  WNT8B; protein Wnt-8b [KO:K00714]
120616643  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
120589260  WNT9B; protein Wnt-9b [KO:K01064]
120618208  WNT10B; protein Wnt-10b [KO:K01357]
120587739  WNT10A; protein Wnt-10a [KO:K01357]
120590369  WNT11; protein Wnt-11 [KO:K01384]
120601159  WNT16; protein Wnt-16 [KO:K01558]
120615046  FZD1; frizzled-1 [KO:K02432]
120587540  FZD7; frizzled-7 [KO:K02432]
120589224  FZD2; frizzled-2 [KO:K02235]
120613253  FZD3; frizzled-3 isoform X1 [KO:K02329]
120590461  FZD4; frizzled-4 [KO:K02354]
120593264  FZD8; frizzled-8 [KO:K02375]
120587587  FZD5; frizzled-5 [KO:K02375]
120595684  FZD6; frizzled-6 [KO:K02376]
120591641  FZD9; frizzled-9 [KO:K02842]
120615989  FZD10; frizzled-10 [KO:K02842]
120614091  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
120593039  DVL3; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
120589630  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
120603713  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
120595639  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
120622065  YWHAQ; 14-3-3 protein theta [KO:K16197]
120621032  YWHAE; 14-3-3 protein epsilon [KO:K06630]
120591800  YWHAG; 14-3-3 protein gamma [KO:K16198]
120601857  YWHAH; 14-3-3 protein eta [KO:K16198]
120586669  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120582202  CTNNB1; catenin beta-1 [KO:K02105]
120590819  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
120583698  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
120620161  AXIN1; axin-1 isoform X1 [KO:K02157]
120600021  AXIN2; LOW QUALITY PROTEIN: axin-2 [KO:K04385]
120616861  uncharacterized protein LOC120616861 [KO:K03213]
120617257  NKD1; protein naked cuticle homolog 1 isoform X1 [KO:K03213]
120586143  NKD2; LOW QUALITY PROTEIN: protein naked cuticle homolog 2 [KO:K03213]
120581289  TCF7; transcription factor 7 isoform X1 [KO:K02620]
120594603  TCF7L1; transcription factor 7-like 1 [KO:K04490]
120609085  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
120591231  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
120595433  MYC; myc proto-oncogene protein [KO:K04377]
120584714  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120607308  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
120596338  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
120592943  SOX2; transcription factor SOX-2 [KO:K16796]
120592716  SNAI2; zinc finger protein SNAI2 [KO:K05706]
120618083  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
120618084  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
120615525  ACTB; actin, cytoplasmic 1 [KO:K05692]
120599974  ACTG1; actin, cytoplasmic 2 [KO:K05692]
120581360  CTNNA1; catenin alpha-1 [KO:K05691]
120594452  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
120609429  CTNNA3; catenin alpha-3 [KO:K05691]
Reference
PMID:22750148
  Authors
Schroeder MC, Halder G
  Title
Regulation of the Hippo pathway by cell architecture and mechanical signals.
  Journal
Semin Cell Dev Biol 23:803-11 (2012)
DOI:10.1016/j.semcdb.2012.06.001
Reference
PMID:21808241
  Authors
Zhao B, Tumaneng K, Guan KL
  Title
The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal.
  Journal
Nat Cell Biol 13:877-83 (2011)
DOI:10.1038/ncb2303
Reference
PMID:21874053
  Authors
Mauviel A, Nallet-Staub F, Varelas X
  Title
Integrating developmental signals: a Hippo in the (path)way.
  Journal
Oncogene 31:1743-56 (2012)
DOI:10.1038/onc.2011.363
Reference
PMID:21084559
  Authors
Zhao B, Li L, Guan KL
  Title
Hippo signaling at a glance.
  Journal
J Cell Sci 123:4001-6 (2010)
DOI:10.1242/jcs.069070
Reference
PMID:20439427
  Authors
Zhao B, Li L, Lei Q, Guan KL
  Title
The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version.
  Journal
Genes Dev 24:862-74 (2010)
DOI:10.1101/gad.1909210
Reference
PMID:23034192
  Authors
Tremblay AM, Camargo FD
  Title
Hippo signaling in mammalian stem cells.
  Journal
Semin Cell Dev Biol 23:818-26 (2012)
DOI:10.1016/j.semcdb.2012.08.001
Reference
PMID:21138973
  Authors
Halder G, Johnson RL
  Title
Hippo signaling: growth control and beyond.
  Journal
Development 138:9-22 (2011)
DOI:10.1242/dev.045500
Reference
PMID:22658639
  Authors
Ramos A, Camargo FD
  Title
The Hippo signaling pathway and stem cell biology.
  Journal
Trends Cell Biol 22:339-46 (2012)
DOI:10.1016/j.tcb.2012.04.006
Reference
PMID:20951342
  Authors
Pan D
  Title
The hippo signaling pathway in development and cancer.
  Journal
Dev Cell 19:491-505 (2010)
DOI:10.1016/j.devcel.2010.09.011
Reference
PMID:21324984
  Authors
Bao Y, Hata Y, Ikeda M, Withanage K
  Title
Mammalian Hippo pathway: from development to cancer and beyond.
  Journal
J Biochem 149:361-79 (2011)
DOI:10.1093/jb/mvr021
Reference
PMID:18955139
  Authors
Zhao B, Lei QY, Guan KL
  Title
The Hippo-YAP pathway: new connections between regulation of organ size and cancer.
  Journal
Curr Opin Cell Biol 20:638-46 (2008)
DOI:10.1016/j.ceb.2008.10.001
Reference
PMID:20945341
  Authors
Chan SW, Lim CJ, Chen L, Chong YF, Huang C, Song H, Hong W
  Title
The Hippo pathway in biological control and cancer development.
  Journal
J Cell Physiol 226:928-39 (2011)
DOI:10.1002/jcp.22435
Reference
PMID:18328423
  Authors
Zeng Q, Hong W
  Title
The emerging role of the hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals.
  Journal
Cancer Cell 13:188-92 (2008)
DOI:10.1016/j.ccr.2008.02.011
Reference
PMID:19846288
  Authors
Badouel C, Garg A, McNeill H
  Title
Herding Hippos: regulating growth in flies and man.
  Journal
Curr Opin Cell Biol 21:837-43 (2009)
DOI:10.1016/j.ceb.2009.09.010
Reference
PMID:17975546
  Authors
Buttitta LA, Edgar BA
  Title
How size is controlled: from Hippos to Yorkies.
  Journal
Nat Cell Biol 9:1225-7 (2007)
DOI:10.1038/ncb1107-1225
Reference
PMID:22683405
  Authors
Liu AM, Wong KF, Jiang X, Qiao Y, Luk JM
  Title
Regulators of mammalian Hippo pathway in cancer.
  Journal
Biochim Biophys Acta 1826:357-64 (2012)
DOI:10.1016/j.bbcan.2012.05.006
Reference
PMID:22830020
  Authors
Fausti F, Di Agostino S, Sacconi A, Strano S, Blandino G
  Title
Hippo and rassf1a Pathways: A Growing Affair.
  Journal
Mol Biol Int 2012:307628 (2012)
DOI:10.1155/2012/307628
Reference
PMID:22895435
  Authors
Halder G, Dupont S, Piccolo S
  Title
Transduction of mechanical and cytoskeletal cues by YAP and TAZ.
  Journal
Nat Rev Mol Cell Biol 13:591-600 (2012)
DOI:10.1038/nrm3416
Reference
PMID:22153608
  Authors
Varelas X, Wrana JL
  Title
Coordinating developmental signaling: novel roles for the Hippo pathway.
  Journal
Trends Cell Biol 22:88-96 (2012)
DOI:10.1016/j.tcb.2011.10.002
Reference
PMID:21376238
  Authors
Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, Kreger BT, Vasioukhin V, Avruch J, Brummelkamp TR, Camargo FD
  Title
Yap1 acts downstream of alpha-catenin to control epidermal proliferation.
  Journal
Cell 144:782-95 (2011)
DOI:10.1016/j.cell.2011.02.031
Related
pathway
pgig04120  Ubiquitin mediated proteolysis
pgig04310  Wnt signaling pathway
pgig04350  TGF-beta signaling pathway
pgig04520  Adherens junction
pgig04530  Tight junction
KO pathway
ko04390   
LinkDB

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