KEGG   PATHWAY: ray04390
Entry
ray04390                    Pathway                                
Name
Hippo signaling pathway - Rousettus aegyptiacus (Egyptian rousette)
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
ray04390  Hippo signaling pathway
ray04390

Other DBs
GO: 0035329
Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107520819  CRB1; protein crumbs homolog 1 [KO:K16681]
107506655  CRB2; LOW QUALITY PROTEIN: protein crumbs homolog 2 [KO:K16681]
107520741  PARD3; partitioning defective 3 homolog [KO:K04237]
107510342  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
107520321  PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
107500856  PARD6G; LOW QUALITY PROTEIN: partitioning defective 6 homolog gamma [KO:K06093]
107510685  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
107501405  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
107508509  PATJ; inaD-like protein [KO:K06092]
107503256  MPP5; LOW QUALITY PROTEIN: MAGUK p55 subfamily member 5 [KO:K06091]
107509861  AMOT; angiomotin isoform X1 [KO:K16819]
107504642  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
107497880  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
107520648  CDH1; LOW QUALITY PROTEIN: cadherin-1 [KO:K05689]
107521420  WTIP; LOW QUALITY PROTEIN: Wilms tumor protein 1-interacting protein [KO:K16682]
107509051  LIM domain-containing protein 1-like [KO:K16682]
107509087  LIM domain-containing protein 1 [KO:K16682]
107498033  AJUBA; LIM domain-containing protein ajuba [KO:K16682]
107520479  NF2; merlin isoform X1 [KO:K16684]
107514072  WWC1; protein KIBRA isoform X1 [KO:K16685]
107518074  FRMD1; FERM domain-containing protein 1 isoform X1 [KO:K16821]
107498122  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
107511444  SAV1; protein salvador homolog 1 [KO:K16686]
107517276  STK3; serine/threonine-protein kinase 3 isoform X1 [KO:K04412]
107515321  RASSF6; ras association domain-containing protein 6 isoform X1 [KO:K09854]
107513391  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
107506800  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107505807  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
107521184  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
107500417  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
107519027  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
107515450  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
107500870  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
107514364  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
107518457  LATS1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
107502926  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
107504023  MOB1B; MOB kinase activator 1B isoform X1 [KO:K06685]
107511165  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
107503728  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
107513247  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
107498968  TP53BP2; apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
107511085  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
107501612  LLGL2; lethal(2) giant larvae protein homolog 2 [KO:K06094]
107507860  SCRIB; protein scribble homolog [KO:K16175]
107505282  DLG1; LOW QUALITY PROTEIN: disks large homolog 1 [KO:K12076]
107518561  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
107503831  DLG3; disks large homolog 3 isoform X1 [KO:K21098]
107509512  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
107518068  DLG5; disks large homolog 5 isoform X1 [KO:K24050]
107504039  CSNK1D; casein kinase I isoform delta isoform X1 [KO:K08959] [EC:2.7.11.1]
107519258  casein kinase I isoform epsilon isoform X1 [KO:K08960] [EC:2.7.11.1]
107511023  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
107497788  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
107510662  TP73; tumor protein p73 [KO:K10148]
107516010  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
107502697  TEAD4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
107505343  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
107498859  TEAD2; transcriptional enhancer factor TEF-4 isoform X1 [KO:K09448]
107497885  TEAD3; transcriptional enhancer factor TEF-5 isoform X1 [KO:K09448]
107502316  CTGF; LOW QUALITY PROTEIN: connective tissue growth factor [KO:K06827]
107501918  GLI2; LOW QUALITY PROTEIN: zinc finger protein GLI2 [KO:K16798]
107515312  AREG; LOW QUALITY PROTEIN: amphiregulin [KO:K09782]
107510062  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
107515334  AFP; alpha-fetoprotein [KO:K16144]
107515323  LOW QUALITY PROTEIN: alpha-fetoprotein-like [KO:K16144]
107510212  ITGB2; integrin beta-2 isoform X1 [KO:K06464]
107500865  FGF1; fibroblast growth factor 1 [KO:K18496]
107505490  TGFB1; transforming growth factor beta-1 [KO:K13375]
107520844  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
107498899  TGFB3; transforming growth factor beta-3 [KO:K13377]
107500589  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
107508791  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
107512669  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
107512663  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
107508935  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
107512852  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
107511771  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
107511521  BMP2; bone morphogenetic protein 2 [KO:K21283]
107509544  BMP4; bone morphogenetic protein 4 [KO:K04662]
107511375  BMP5; bone morphogenetic protein 5 [KO:K04663]
107507206  BMP6; bone morphogenetic protein 6 [KO:K16620]
107500087  BMP7; bone morphogenetic protein 7 [KO:K16621]
107508332  BMP8B; LOW QUALITY PROTEIN: bone morphogenetic protein 8B [KO:K16622]
107508337  bone morphogenetic protein 8B-like [KO:K16622]
107517077  LOW QUALITY PROTEIN: bone morphogenetic protein 8B-like [KO:K16622]
107500783  GDF5; growth/differentiation factor 5 [KO:K04664]
107500339  GDF6; growth/differentiation factor 6 [KO:K20012]
107510822  GDF7; LOW QUALITY PROTEIN: growth/differentiation factor 7 [KO:K20013]
107520134  AMH; LOW QUALITY PROTEIN: muellerian-inhibiting factor [KO:K04665]
107509897  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
107510637  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
107519367  BMPR2; LOW QUALITY PROTEIN: bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
107520351  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
107512890  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
107498274  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
107514294  WNT1; proto-oncogene Wnt-1 [KO:K03209]
107505364  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
107499803  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
107509667  WNT3A; protein Wnt-3a [KO:K00312]
107508173  WNT3; proto-oncogene Wnt-3 [KO:K00312]
107513057  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
107503411  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
107500582  WNT5B; protein Wnt-5b [KO:K00444]
107516780  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
107505517  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
107502411  WNT7A; protein Wnt-7a [KO:K00572]
107518710  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
107499773  WNT8B; protein Wnt-8b [KO:K00714]
107509675  WNT9A; protein Wnt-9a [KO:K01064]
107508172  WNT9B; protein Wnt-9b [KO:K01064]
107514289  WNT10B; protein Wnt-10b [KO:K01357]
107516694  WNT10A; protein Wnt-10a [KO:K01357]
107519202  WNT11; LOW QUALITY PROTEIN: protein Wnt-11 [KO:K01384]
107500238  WNT16; protein Wnt-16 [KO:K01558]
107519374  FZD7; frizzled-7 [KO:K02432]
107500880  FZD1; frizzled-1 [KO:K02432]
107508108  FZD2; frizzled-2 [KO:K02235]
107510778  FZD3; frizzled-3 isoform X1 [KO:K02329]
107518567  FZD4; frizzled-4 [KO:K02354]
107505121  FZD8; frizzled-8 [KO:K02375]
107505167  FZD5; frizzled-5 [KO:K02375]
107512212  FZD6; frizzled-6 [KO:K02376]
107511767  FZD9; frizzled-9 [KO:K02842]
107511534  FZD10; frizzled-10 [KO:K02842]
107507013  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
107509513  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
107510646  DVL1; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
107512228  14-3-3 protein zeta/delta [KO:K16197]
107514565  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
107498267  YWHAQ; 14-3-3 protein theta [KO:K16197]
107507733  YWHAE; 14-3-3 protein epsilon [KO:K06630]
107511797  YWHAG; 14-3-3 protein gamma [KO:K16198]
107502395  YWHAH; 14-3-3 protein eta [KO:K16198]
107517741  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107519993  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
107500934  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
107512008  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
107506131  AXIN1; axin-1 isoform X1 [KO:K02157]
107510301  AXIN2; axin-2 isoform X1 [KO:K04385]
107512247  NKD1; protein naked cuticle homolog 1 [KO:K03213]
107506797  TCF7; transcription factor 7 isoform X1 [KO:K02620]
107506285  TCF7L1; transcription factor 7-like 1 [KO:K04490]
107511705  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
107511497  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
107506202  MYC; myc proto-oncogene protein [KO:K04377]
107503391  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
107513450  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
107501938  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
107507031  SOX2; transcription factor SOX-2 [KO:K16796]
107514045  SNAI2; zinc finger protein SNAI2 [KO:K05706]
107504640  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
107504641  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
107520262  ACTG1; actin, cytoplasmic 2 [KO:K05692]
107515934  ACTB; actin, cytoplasmic 1 [KO:K05692]
107518703  CTNNA1; catenin alpha-1 [KO:K05691]
107499343  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
107510357  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
ray04120  Ubiquitin mediated proteolysis
ray04310  Wnt signaling pathway
ray04350  TGF-beta signaling pathway
ray04520  Adherens junction
ray04530  Tight junction
KO pathway
ko04390   
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