KEGG   PATHWAY: ocu04390
Entry
ocu04390                    Pathway                                
Name
Hippo signaling pathway - Oryctolagus cuniculus (rabbit)
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
ocu04390  Hippo signaling pathway
ocu04390

Other DBs
GO: 0035329
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100341214  protein crumbs homolog 2 isoform X1 [KO:K16681]
100339170  protein crumbs homolog 1 isoform X1 [KO:K16681]
100345030  partitioning defective 3 homolog isoform X1 [KO:K04237]
100353321  partitioning defective 6 homolog beta [KO:K06093]
100350899  partitioning defective 6 homolog alpha isoform X2 [KO:K06093]
100349557  partitioning defective 6 homolog gamma [KO:K06093]
100009538  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
100348584  protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
100356380  inaD-like protein [KO:K06092]
100340603  PALS1; protein PALS1 [KO:K06091]
100358386  angiomotin isoform X1 [KO:K16819]
100341323  transcriptional coactivator YAP1 isoform X1 [KO:K16687]
100355214  WW domain-containing transcription regulator protein 1 [KO:K16820]
100356548  cadherin-1 [KO:K05689]
100358827  Wilms tumor protein 1-interacting protein isoform X1 [KO:K16682]
100359157  LIM domain-containing protein ajuba isoform X1 [KO:K16682]
100356027  Wilms tumor protein 1-interacting protein [KO:K16682]
100351579  LIM domain-containing protein 1 [KO:K16682]
100357691  merlin isoform X2 [KO:K16684]
100358939  protein KIBRA isoform X2 [KO:K16685]
100352529  FERM domain-containing protein 6 isoform X1 [KO:K16822]
100350937  protein salvador homolog 1 isoform X2 [KO:K16686]
100357564  serine/threonine-protein kinase 3 isoform X1 [KO:K04412]
100344930  ras association domain-containing protein 6 isoform X1 [KO:K09854]
100340832  ras association domain-containing protein 1 isoform X3 [KO:K09850]
100009252  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100009300  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100355092  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100355758  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
100328617  PPP2R2C; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform [KO:K04354]
100009139  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
100328616  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
100348286  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
100349799  LOW QUALITY PROTEIN: serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
100341222  serine/threonine-protein kinase LATS1 isoform X1 [KO:K08791] [EC:2.7.11.1]
100356876  serine/threonine-protein kinase LATS2 isoform X1 [KO:K08791] [EC:2.7.11.1]
100348844  MOB kinase activator 1B [KO:K06685]
100349312  MOB kinase activator 1A [KO:K06685]
100009587  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100009298  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100353054  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100349267  apoptosis-stimulating of p53 protein 2 [KO:K16823]
103345790  LLGL scribble cell polarity complex component 2 isoform X1 [KO:K06094]
100339253  disks large homolog 1 isoform X8 [KO:K12076]
100345988  disks large homolog 2 isoform X28 [KO:K12075]
100349185  disks large homolog 3 isoform X7 [KO:K21098]
100339587  disks large homolog 4 isoform X12 [KO:K11828]
100354463  disks large homolog 5 isoform X1 [KO:K24050]
100338879  casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
100341681  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
100340737  F-box/WD repeat-containing protein 11 isoform X4 [KO:K03362]
100350519  F-box/WD repeat-containing protein 1A isoform X4 [KO:K03362]
100357703  bcl-2-binding component 3 [KO:K10132]
100359304  transcriptional enhancer factor TEF-5 [KO:K09448]
100341523  transcriptional enhancer factor TEF-3 isoform X2 [KO:K09448]
100349978  transcriptional enhancer factor TEF-1 isoform X10 [KO:K09448]
100352383  transcriptional enhancer factor TEF-4 isoform X1 [KO:K09448]
100008638  CCN2; CCN family member 2 [KO:K06827]
100359289  zinc finger protein GLI2 [KO:K16798]
100354550  amphiregulin [KO:K09782]
103346801  baculoviral IAP repeat-containing protein 5 [KO:K08731]
100345865  alpha-fetoprotein [KO:K16144]
103350776  alpha-fetoprotein isoform X1 [KO:K16144]
100339049  integrin beta-2 [KO:K06464]
100328898  FGF1; fibroblast growth factor 1 [KO:K18496]
100352301  LOW QUALITY PROTEIN: transforming growth factor beta-1 proprotein [KO:K13375]
103345448  transforming growth factor beta-1 proprotein isoform X9 [KO:K13375]
100008645  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
100009371  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
100358982  transforming growth factor beta-3 proprotein [KO:K13377]
100345812  TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100344335  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
100338818  mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
100359137  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100346303  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100342294  mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100009588  plasminogen activator inhibitor 1 [KO:K03982]
100009349  BMP2; bone morphogenetic protein 2 precursor [KO:K21283]
100009569  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
100344917  bone morphogenetic protein 5 [KO:K04663]
100354948  bone morphogenetic protein 6 [KO:K16620]
100008826  bone morphogenetic protein 7 [KO:K16621]
103350213  bone morphogenetic protein 8B isoform X1 [KO:K16622]
100341360  bone morphogenetic protein 8B isoform X1 [KO:K16622]
100328897  GDF5; growth/differentiation factor 5 precursor [KO:K04664]
100355026  growth/differentiation factor 6 [KO:K20012]
100339215  growth/differentiation factor 7 [KO:K20013]
100350518  bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100351275  bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
100350246  bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
100341544  mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
100347305  DNA-binding protein inhibitor ID-1 [KO:K04680]
100350879  DNA-binding protein inhibitor ID-2 [KO:K17693]
100354018  proto-oncogene Wnt-1 isoform X1 [KO:K03209]
100126569  WNT2; protein Wnt-2 precursor [KO:K00182]
100349847  protein Wnt-2b isoform X1 [KO:K00182]
100009033  proto-oncogene Wnt-3 isoform X1 [KO:K00312]
100354583  LOW QUALITY PROTEIN: protein Wnt-3a [KO:K00312]
100303773  protein Wnt-4 isoform X2 [KO:K00408]
100009381  WNT5A; protein Wnt-5a precursor [KO:K00444]
100349579  protein Wnt-5b [KO:K00444]
100348986  protein Wnt-6 [KO:K00445]
100355697  protein Wnt-7a [KO:K00572]
100342870  protein Wnt-8a [KO:K00714]
100357933  protein Wnt-8b isoform X1 [KO:K00714]
100353559  protein Wnt-9b [KO:K01064]
100352227  protein Wnt-9a [KO:K01064]
100351316  protein Wnt-10b [KO:K01357]
100352839  protein Wnt-10a [KO:K01357]
100009030  WNT11; protein Wnt-11 [KO:K01384]
100353090  protein Wnt-16 [KO:K01558]
103348917  frizzled-7 [KO:K02432]
100356368  frizzled-1 [KO:K02432]
100350521  frizzled-2 [KO:K02235]
100339544  frizzled-3 isoform X1 [KO:K02329]
100342099  frizzled-4 [KO:K02354]
103352372  frizzled-8 [KO:K02375]
100352919  frizzled-5 [KO:K02375]
100344394  frizzled-6 [KO:K02376]
100345803  frizzled-9 [KO:K02842]
100358367  segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
100339336  segment polarity protein dishevelled homolog DVL-2 isoform X2 [KO:K02353]
127489271  segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100358299  14-3-3 protein beta/alpha [KO:K16197]
100008930  YWHAQ; 14-3-3 protein theta [KO:K16197]
100342694  14-3-3 protein zeta/delta [KO:K16197]
100358813  14-3-3 protein epsilon isoform X4 [KO:K06630]
100328734  YWHAH; 14-3-3 protein eta [KO:K16198]
100354276  14-3-3 protein gamma [KO:K16198]
127488492  14-3-3 protein gamma [KO:K16198]
100348842  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100125985  catenin beta-1 [KO:K02105]
100353976  adenomatous polyposis coli protein isoform X1 [KO:K02085]
103346018  LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
127485674  adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
100348127  axin-1 isoform X1 [KO:K02157]
100339765  axin-2 [KO:K04385]
100356844  protein naked cuticle homolog 1 [KO:K03213]
127482783  protein naked cuticle homolog 1-like [KO:K03213]
100339216  transcription factor 7 isoform X1 [KO:K02620]
100340471  transcription factor 7-like 1 isoform X1 [KO:K04490]
100358378  transcription factor 7-like 2 isoform X1 [KO:K04491]
100352691  lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100327265  MYC; myc proto-oncogene protein [KO:K04377]
100009036  G1/S-specific cyclin-D2 [KO:K10151]
100009038  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100341629  transcription factor SOX-2 [KO:K16796]
100346095  zinc finger protein SNAI2 [KO:K05706]
100340120  baculoviral IAP repeat-containing protein 3 [KO:K16060]
100338118  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
100008822  actin, cytoplasmic 1 [KO:K05692]
100009272  ACTB; actin, cytoplasmic 1 [KO:K05692]
100341037  LOW QUALITY PROTEIN: actin, cytoplasmic 2-like [KO:K05692]
100343241  catenin alpha-3 isoform X1 [KO:K05691]
100328952  CTNNA1; catenin alpha-1 [KO:K05691]
100352391  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
ocu04120  Ubiquitin mediated proteolysis
ocu04310  Wnt signaling pathway
ocu04350  TGF-beta signaling pathway
ocu04520  Adherens junction
ocu04530  Tight junction
KO pathway
ko04390   
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