KEGG   PATHWAY: oas04390
Entry
oas04390                    Pathway                                
Name
Hippo signaling pathway - Ovis aries (sheep)
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
oas04390  Hippo signaling pathway
oas04390

Other DBs
GO: 0035329
Organism
Ovis aries (sheep) [GN:oas]
Gene
101106957  CRB1; protein crumbs homolog 1 [KO:K16681]
101113926  CRB2; protein crumbs homolog 2 [KO:K16681]
101110782  PARD3; partitioning defective 3 homolog isoform X3 [KO:K04237]
101118720  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
101114893  PARD6A; partitioning defective 6 homolog alpha isoform X2 [KO:K06093]
101121649  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
101122295  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
101118322  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
101106044  PATJ; inaD-like protein isoform X2 [KO:K06092]
101113152  PALS1; protein PALS1 isoform X1 [KO:K06091]
101108810  AMOT; angiomotin isoform X1 [KO:K16819]
100913160  YAP1; transcriptional coactivator YAP1 [KO:K16687]
101120978  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
101119747  CDH1; cadherin-1 [KO:K05689]
101119260  LIMD1; LIM domain-containing protein 1 [KO:K16682]
101112921  WTIP; Wilms tumor protein 1-interacting protein isoform X1 [KO:K16682]
101102150  AJUBA; LIM domain-containing protein ajuba isoform X1 [KO:K16682]
101107995  NF2; merlin isoform X1 [KO:K16684]
101110932  LOW QUALITY PROTEIN: merlin [KO:K16684]
101117418  WWC1; protein KIBRA [KO:K16685]
105606080  FRMD1; FERM domain-containing protein 1 isoform X2 [KO:K16821]
101106265  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
101104666  SAV1; protein salvador homolog 1 [KO:K16686]
101106085  STK3; serine/threonine-protein kinase 3 isoform X2 [KO:K04412]
101102984  RASSF6; ras association domain-containing protein 6 isoform X5 [KO:K09854]
100302080  RASSF1; ras association domain-containing protein 1 [KO:K09850]
101114930  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
443009  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
101108352  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
101115302  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101108511  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
101109519  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
114111443  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
101110299  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X5 [KO:K04354]
101102148  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
101113409  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X6 [KO:K04354]
101117941  LATS2; serine/threonine-protein kinase LATS2 isoform X1 [KO:K08791] [EC:2.7.11.1]
101122867  LATS1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
101115526  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
101123123  MOB1B; MOB kinase activator 1B isoform X2 [KO:K06685]
101119264  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101123197  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101106284  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101108587  TP53BP2; apoptosis-stimulating of p53 protein 2 isoform X3 [KO:K16823]
101120930  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X2 [KO:K06094]
101120426  LLGL2; LLGL scribble cell polarity complex component 2 isoform X1 [KO:K06094]
101111976  SCRIB; protein scribble homolog isoform X8 [KO:K16175]
101103028  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
101104867  DLG2; disks large homolog 2 isoform X12 [KO:K12075]
101102123  DLG3; disks large homolog 3 isoform X6 [KO:K21098]
101116743  DLG4; disks large homolog 4 isoform X8 [KO:K11828]
101110731  DLG5; disks large homolog 5 isoform X2 [KO:K24050]
100171396  CSNK1D; casein kinase I isoform X2 [KO:K08959] [EC:2.7.11.1]
443240  CSNK1E; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
101101939  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
101107136  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
114115342  F-box/WD repeat-containing protein 11-like [KO:K03362]
101118974  TP73; tumor protein p73 [KO:K10148]
101123490  BBC3; bcl-2-binding component 3 isoform X2 [KO:K10132]
101112975  TEAD4; transcriptional enhancer factor TEF-3 isoform X6 [KO:K09448]
101105097  TEAD2; transcriptional enhancer factor TEF-4 isoform X2 [KO:K09448]
101120947  TEAD1; transcriptional enhancer factor TEF-1 isoform X3 [KO:K09448]
101122474  TEAD3; transcriptional enhancer factor TEF-5 isoform X1 [KO:K09448]
114113600  LOW QUALITY PROTEIN: transcriptional enhancer factor TEF-4-like [KO:K09448]
100303607  CCN2; CCN family member 2 precursor [KO:K06827]
101114169  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
443427  AREG; amphiregulin isoform X2 [KO:K09782]
101123390  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
101103646  AFP; alpha-fetoprotein isoform X2 [KO:K16144]
494433  ITGB2; integrin beta-2 precursor [KO:K06464]
101109353  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
443417  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
554322  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
554323  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
554326  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
494191  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
101111414  SMAD7; mothers against decapentaplegic homolog 7 isoform X2 [KO:K19631]
101114231  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
443169  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
443171  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100381267  SERPINE1; plasminogen activator inhibitor 1 precursor [KO:K03982]
101117688  BMP2; bone morphogenetic protein 2 [KO:K21283]
443502  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
101107231  BMP5; bone morphogenetic protein 5 [KO:K04663]
443174  BMP6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
443175  BMP7; bone morphogenetic protein 7 precursor [KO:K16621]
105604271  BMP8B; bone morphogenetic protein 8B [KO:K16622]
101120626  bone morphogenetic protein 8B [KO:K16622]
101116499  GDF5; growth/differentiation factor 5 [KO:K04664]
101108925  GDF6; growth/differentiation factor 6 isoform X1 [KO:K20012]
106990980  GDF7; growth/differentiation factor 7 [KO:K20013]
101121773  AMH; muellerian-inhibiting factor precursor [KO:K04665]
101112282  BMPR1A; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:2.7.11.30]
443454  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
101103793  BMPR2; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:2.7.11.30]
443229  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
101111650  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101115522  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101103389  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101116782  WNT2B; protein Wnt-2b [KO:K00182]
100126577  WNT2; protein Wnt-2 precursor [KO:K00182]
101120096  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101123374  WNT3A; protein Wnt-3a [KO:K00312]
101122423  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
101121415  WNT5B; protein Wnt-5b isoform X2 [KO:K00444]
101109745  WNT5A; protein Wnt-5a [KO:K00444]
101111785  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
101109531  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
114109341  WNT7A; protein Wnt-7a [KO:K00572]
101121814  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
101108044  WNT8A; protein Wnt-8a [KO:K00714]
121820714  WNT9B; protein Wnt-9b [KO:K01064]
101102060  WNT9A; protein Wnt-9a [KO:K01064]
101102299  WNT10B; protein Wnt-10b [KO:K01357]
101113129  WNT10A; protein Wnt-10a [KO:K01357]
101111048  WNT11; protein Wnt-11 [KO:K01384]
101103229  WNT16; protein Wnt-16 [KO:K01558]
101103546  FZD7; frizzled-7 [KO:K02432]
101112309  FZD1; frizzled-1 [KO:K02432]
780481  FZD2; frizzled-2 [KO:K02235]
780482  FZD3; frizzled-3 isoform X1 [KO:K02329]
114110622  liprin-alpha-1-like [KO:K02329]
101101932  FZD4; frizzled-4 [KO:K02354]
101118762  FZD5; frizzled-5 [KO:K02375]
114117561  FZD8; frizzled-8 [KO:K02375]
101122197  FZD6; frizzled-6 [KO:K02376]
101114236  FZD9; frizzled-9 [KO:K02842]
101118991  FZD10; frizzled-10 [KO:K02842]
101117599  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X2 [KO:K02353]
101104259  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
101107926  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X2 [KO:K02353]
101110165  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
780452  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
101117574  YWHAQ; 14-3-3 protein theta [KO:K16197]
101105269  14-3-3 protein zeta/delta-like [KO:K16197]
101115653  14-3-3 protein theta-like [KO:K16197]
106991506  14-3-3 protein zeta/delta-like [KO:K16197]
114115591  14-3-3 protein zeta/delta-like [KO:K16197]
443300  YWHAE; 14-3-3 protein epsilon isoform X2 [KO:K06630]
101116012  YWHAG; 14-3-3 protein gamma [KO:K16198]
443301  YWHAH; 14-3-3 protein eta isoform X2 [KO:K16198]
100169938  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
100294600  CTNNB1; catenin beta-1 [KO:K02105]
101115458  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
101104664  APC; adenomatous polyposis coli protein isoform X3 [KO:K02085]
101122656  AXIN1; axin-1 isoform X1 [KO:K02157]
101109815  AXIN2; axin-2 isoform X1 [KO:K04385]
101116855  NKD1; protein naked cuticle homolog 1 [KO:K03213]
114118764  NKD2; protein naked cuticle homolog 2 isoform X1 [KO:K03213]
101101980  TCF7; transcription factor 7 isoform X6 [KO:K02620]
100913162  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
101118068  TCF7L2; transcription factor 7-like 2 isoform X19 [KO:K04491]
780521  LEF1; lymphoid enhancer-binding factor 1 isoform X8 [KO:K04492]
443447  MYC; myc proto-oncogene protein [KO:K04377]
100144763  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100147799  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100147798  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
101110563  SOX2; transcription factor SOX-2 [KO:K16796]
100127220  SNAI2; zinc finger protein SNAI2 [KO:K05706]
101119930  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
101120189  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
443340  ACTG1; actin, cytoplasmic 2 [KO:K05692]
443052  ACTB; actin, cytoplasmic 1 [KO:K05692]
101123346  CTNNA3; catenin alpha-3 isoform X5 [KO:K05691]
101112313  CTNNA1; catenin alpha-1 isoform X3 [KO:K05691]
101121501  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
114110421  LOW QUALITY PROTEIN: catenin alpha-1-like [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
oas04120  Ubiquitin mediated proteolysis
oas04310  Wnt signaling pathway
oas04350  TGF-beta signaling pathway
oas04520  Adherens junction
oas04530  Tight junction
KO pathway
ko04390   
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