KEGG   PATHWAY: hhv04390
Entry
hhv04390                    Pathway                                
Name
Hippo signaling pathway - Hyaena hyaena (striped hyena)
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
hhv04390  Hippo signaling pathway
hhv04390

Other DBs
GO: 0035329
Organism
Hyaena hyaena (striped hyena) [GN:hhv]
Gene
120236320  CRB2; protein crumbs homolog 2 [KO:K16681]
120245584  CRB1; protein crumbs homolog 1 [KO:K16681]
120247429  PARD3; partitioning defective 3 homolog isoform X1 [KO:K04237]
120224644  PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
120240945  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
120230457  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
120242512  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
120234619  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
120247415  PATJ; inaD-like protein [KO:K06092]
120237432  MPP5; MAGUK p55 subfamily member 5 isoform X1 [KO:K06091]
120241980  AMOT; angiomotin [KO:K16819]
120219679  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
120237635  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
120225176  CDH1; cadherin-1 [KO:K05689]
120229295  LIMD1; LIM domain-containing protein 1 isoform X1 [KO:K16682]
120240435  AJUBA; LIM domain-containing protein ajuba [KO:K16682]
120231689  Wilms tumor protein 1-interacting protein [KO:K16682]
120227162  NF2; merlin isoform X1 [KO:K16684]
120242135  WWC1; protein KIBRA isoform X1 [KO:K16685]
120248688  FRMD1; FERM domain-containing protein 1 [KO:K16821]
120247979  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
120220275  SAV1; protein salvador homolog 1 [KO:K16686]
120247534  STK3; serine/threonine-protein kinase 3 [KO:K04412]
120231114  RASSF6; ras association domain-containing protein 6 isoform X1 [KO:K09854]
120229298  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
120238508  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120223033  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120229915  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
120222367  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120244090  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
120221673  uncharacterized protein LOC120221673 [KO:K04354]
120231861  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
120245371  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
120248361  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
120237568  LATS1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
120247206  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
120237004  MOB1A; MOB kinase activator 1A [KO:K06685]
120244973  MOB1B; MOB kinase activator 1B [KO:K06685]
120233909  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
120239251  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
120235890  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
120234137  TP53BP2; apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
120228258  LLGL2; LLGL scribble cell polarity complex component 2 [KO:K06094]
120228727  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
120246502  SCRIB; protein scribble homolog isoform X1 [KO:K16175]
120244365  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
120231631  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
120246041  DLG3; disks large homolog 3 isoform X1 [KO:K21098]
120231439  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
120237302  DLG5; disks large homolog 5 isoform X1 [KO:K24050]
120228182  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
120241158  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
120243193  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
120234082  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
120220900  tumor protein p73-like [KO:K10148]
120244480  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
120237528  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
120233832  TEAD3; transcriptional enhancer factor TEF-5 isoform X1 [KO:K09448]
120234469  TEAD4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
120241587  TEAD2; transcriptional enhancer factor TEF-4 isoform X1 [KO:K09448]
120237246  CCN2; CCN family member 2 [KO:K06827]
120233573  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
120231060  AREG; amphiregulin [KO:K09782]
120228299  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
120231057  alpha-fetoprotein-like [KO:K16144]
120231108  LOW QUALITY PROTEIN: alpha-fetoprotein [KO:K16144]
120248676  ITGB2; LOW QUALITY PROTEIN: integrin beta-2 [KO:K06464]
120234333  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
120243258  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
120221741  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
120231992  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
120233513  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
120224680  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
120229723  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
120229672  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120221278  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
120229684  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
120239343  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
120226397  BMP2; bone morphogenetic protein 2 [KO:K21283]
120237282  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
120239796  BMP5; bone morphogenetic protein 5 [KO:K04663]
120246799  BMP6; bone morphogenetic protein 6 [KO:K16620]
120234897  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
120226391  BMP8B; bone morphogenetic protein 8B [KO:K16622]
120226394  bone morphogenetic protein 8B [KO:K16622]
120242806  GDF5; growth/differentiation factor 5 [KO:K04664]
120246125  GDF6; growth/differentiation factor 6 [KO:K20012]
120222386  GDF7; growth/differentiation factor 7 [KO:K20013]
120242319  AMH; muellerian-inhibiting factor [KO:K04665]
120232786  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
120237845  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
120248921  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
120246680  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
120235438  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
120231166  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
120223020  WNT1; proto-oncogene Wnt-1 [KO:K03209]
120224618  WNT2; protein Wnt-2 [KO:K00182]
120247131  WNT2B; protein Wnt-2b [KO:K00182]
120244272  WNT3; proto-oncogene Wnt-3 [KO:K00312]
120222424  WNT3A; protein Wnt-3a [KO:K00312]
120232996  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
120234450  WNT5B; protein Wnt-5b [KO:K00444]
120248968  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
120232462  WNT6; protein Wnt-6 [KO:K00445]
120235209  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
120247152  WNT7A; protein Wnt-7a [KO:K00572]
120243200  WNT8B; protein Wnt-8b [KO:K00714]
120220758  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
120244261  WNT9B; protein Wnt-9b [KO:K01064]
120222452  WNT9A; protein Wnt-9a [KO:K01064]
120232455  WNT10A; protein Wnt-10a [KO:K01357]
120223019  WNT10B; protein Wnt-10b [KO:K01357]
120229583  WNT11; protein Wnt-11 [KO:K01384]
120224601  WNT16; protein Wnt-16 [KO:K01558]
120243796  FZD1; frizzled-1 [KO:K02432]
120248935  FZD7; frizzled-7 isoform X1 [KO:K02432]
120222268  FZD2; frizzled-2 [KO:K02235]
120220149  FZD3; frizzled-3 isoform X1 [KO:K02329]
120246706  FZD4; frizzled-4 [KO:K02354]
120237396  FZD5; frizzled-5 [KO:K02375]
120225614  FZD8; frizzled-8 [KO:K02375]
120232875  FZD6; frizzled-6 isoform X1 [KO:K02376]
120243450  FZD10; frizzled-10 [KO:K02842]
120239316  FZD9; frizzled-9 [KO:K02842]
120238099  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
120231441  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
120242533  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
120232842  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
120231148  YWHAQ; 14-3-3 protein theta [KO:K16197]
120242603  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
120245536  YWHAE; 14-3-3 protein epsilon [KO:K06630]
120227869  YWHAH; 14-3-3 protein eta [KO:K16198]
120239308  YWHAG; 14-3-3 protein gamma [KO:K16198]
120242922  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120230647  CTNNB1; catenin beta-1 [KO:K02105]
120242387  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
120236758  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
120225169  AXIN1; axin-1 isoform X1 [KO:K02157]
120234189  AXIN2; axin-2 [KO:K04385]
120238379  NKD1; protein naked cuticle homolog 1 [KO:K03213]
120238500  TCF7; transcription factor 7 isoform X1 [KO:K02620]
120220478  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
120235337  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
120236146  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
120240874  MYC; myc proto-oncogene protein [KO:K04377]
120233874  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120247732  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
120238692  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
120238535  SOX2; transcription factor SOX-2 [KO:K16796]
120221780  SNAI2; zinc finger protein SNAI2 [KO:K05706]
120219677  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 3-like [KO:K16060]
120219681  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
120228024  ACTB; actin, cytoplasmic 1 [KO:K05692]
120228303  ACTG1; actin, cytoplasmic 2 [KO:K05692]
120232507  CTNNA3; catenin alpha-3 [KO:K05691]
120226688  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
120235700  CTNNA2; catenin alpha-2 isoform X1 [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
hhv04120  Ubiquitin mediated proteolysis
hhv04310  Wnt signaling pathway
hhv04350  TGF-beta signaling pathway
hhv04520  Adherens junction
hhv04530  Tight junction
KO pathway
ko04390   
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