KEGG   PATHWAY: ccad04390
Entry
ccad04390                   Pathway                                
Name
Hippo signaling pathway - Cervus canadensis (wapiti)
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
ccad04390  Hippo signaling pathway
ccad04390

Other DBs
GO: 0035329
Organism
Cervus canadensis (wapiti) [GN:ccad]
Gene
122442142  CRB2; protein crumbs homolog 2 [KO:K16681]
122452311  CRB1; protein crumbs homolog 1 [KO:K16681]
122448866  PARD3; partitioning defective 3 homolog isoform X1 [KO:K04237]
122451294  LOW QUALITY PROTEIN: partitioning defective 3 homolog [KO:K04237]
122420789  PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
122448703  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
122425525  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
122452072  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
122444946  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
122436893  PATJ; InaD-like protein isoform X1 [KO:K06092]
122443772  PALS1; protein PALS1 isoform X1 [KO:K06091]
122434532  AMOT; angiomotin [KO:K16819]
122450361  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
122445061  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
122421517  CDH1; cadherin-1 isoform X1 [KO:K05689]
122420122  Wilms tumor protein 1-interacting protein isoform X1 [KO:K16682]
122424349  LIMD1; LIM domain-containing protein 1 [KO:K16682]
122443212  AJUBA; LIM domain-containing protein ajuba isoform X1 [KO:K16682]
122421213  NF2; merlin isoform X1 [KO:K16684]
122439584  WWC1; protein KIBRA [KO:K16685]
122434046  FRMD1; FERM domain-containing protein 1 isoform X1 [KO:K16821]
122443480  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
122443471  SAV1; protein salvador homolog 1 [KO:K16686]
122451521  STK3; serine/threonine-protein kinase 3 [KO:K04412]
122428440  RASSF6; ras association domain-containing protein 6 isoform X1 [KO:K09854]
122425098  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
122439917  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
122432467  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
122450320  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
122435910  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
122420615  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
122429249  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform-like [KO:K04354]
122439750  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
122431987  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
122428377  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
122447168  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
122434007  LATS1; serine/threonine-protein kinase LATS1 isoform X1 [KO:K08791] [EC:2.7.11.1]
122441494  MOB1A; MOB kinase activator 1A [KO:K06685]
122428471  MOB1B; MOB kinase activator 1B [KO:K06685]
122440096  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
122430818  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
122441910  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
122423576  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
122435753  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
122452393  TP53BP2; apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
122436759  LLGL2; LLGL scribble cell polarity complex component 2 isoform X1 [KO:K06094]
122443969  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
122451400  SCRIB; protein scribble homolog isoform X1 [KO:K16175]
122444689  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
122430672  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
122434859  DLG3; disks large homolog 3 isoform X1 [KO:K21098]
122446171  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
122446343  DLG5; disks large homolog 5 isoform X1 [KO:K24050]
122438820  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
122423369  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
122454491  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
122446012  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
122452389  TP73; tumor protein P73 [KO:K10148]
122421529  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
122420780  TEAD2; transcriptional enhancer factor TEF-4 isoform X1 [KO:K09448]
122429201  TEAD3; transcriptional enhancer factor TEF-5 isoform X1 [KO:K09448]
122449576  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
122423370  TEAD4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
122420638  transcriptional enhancer factor TEF-4-like [KO:K09448]
122434030  CCN2; CCN family member 2 [KO:K06827]
122453941  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
122428214  AREG; amphiregulin [KO:K09782]
122437556  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
122428352  alpha-fetoprotein [KO:K16144]
122445429  ITGB2; integrin beta-2 [KO:K06464]
122439770  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
122420314  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
122452400  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122443885  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
122453210  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
122424266  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
122425528  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
122425874  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
122443073  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
122425381  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
122433325  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
122448237  BMP2; bone morphogenetic protein 2 [KO:K21283]
122443659  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
122429835  BMP5; bone morphogenetic protein 5 [KO:K04663]
122429664  BMP6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
122448667  BMP7; bone morphogenetic protein 7 [KO:K16621]
122437173  BMP8B; bone morphogenetic protein 8B [KO:K16622]
122437180  BMP8A; bone morphogenetic protein 8A [KO:K16622]
122447965  GDF5; growth/differentiation factor 5 [KO:K04664]
122451500  GDF6; growth/differentiation factor 6 [KO:K20012]
122442026  GDF7; growth/differentiation factor 7 isoform X1 [KO:K20013]
122440168  AMH; muellerian-inhibiting factor isoform X1 [KO:K04665]
122446247  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
122422280  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
122426765  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
122451988  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
122448668  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
122442095  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
122427439  WNT1; proto-oncogene Wnt-1 [KO:K03209]
122436531  WNT2B; protein Wnt-2b [KO:K00182]
122438339  WNT2; protein Wnt-2 [KO:K00182]
122439332  WNT3A; protein Wnt-3a [KO:K00312]
122440141  WNT3; proto-oncogene Wnt-3 [KO:K00312]
122426808  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
122423100  WNT5B; protein Wnt-5b [KO:K00444]
122424423  WNT5A; protein Wnt-5a [KO:K00444]
122426705  WNT6; protein Wnt-6 [KO:K00445]
122423904  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
122425114  WNT7A; protein Wnt-7a [KO:K00572]
122439209  WNT8A; protein Wnt-8a isoform X1 [KO:K00714]
122446043  WNT8B; protein Wnt-8b [KO:K00714]
122440612  WNT9A; protein Wnt-9a [KO:K01064]
122440147  WNT9B; protein Wnt-9b [KO:K01064]
122426703  WNT10A; protein Wnt-10a [KO:K01357]
122427584  WNT10B; protein Wnt-10b [KO:K01357]
122449784  WNT11; protein Wnt-11 [KO:K01384]
122438578  WNT16; protein Wnt-16 [KO:K01558]
122426021  FZD7; frizzled-7 [KO:K02432]
122438068  FZD1; frizzled-1 [KO:K02432]
122440461  FZD2; frizzled-2 [KO:K02235]
122453133  FZD3; frizzled-3 isoform X1 [KO:K02329]
122430895  FZD4; frizzled-4 [KO:K02354]
122448204  FZD8; frizzled-8 [KO:K02375]
122426066  FZD5; frizzled-5 [KO:K02375]
122451193  FZD6; frizzled-6 [KO:K02376]
122432799  FZD9; frizzled-9 [KO:K02842]
122454464  FZD10; frizzled-10 [KO:K02842]
122446196  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
122452413  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
122444865  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
122421214  14-3-3 protein zeta/delta-like [KO:K16197]
122447948  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
122442084  YWHAQ; 14-3-3 protein theta [KO:K16197]
122450884  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
122435408  14-3-3 protein theta-like [KO:K16197]
122435407  14-3-3 protein theta-like [KO:K16197]
122453085  14-3-3 protein beta/alpha-like [KO:K16197]
122453084  14-3-3 protein zeta/delta-like [KO:K16197]
122453372  14-3-3 protein zeta/delta-like [KO:K16197]
122453373  14-3-3 protein beta/alpha-like [KO:K16197]
122453072  14-3-3 protein zeta/delta-like [KO:K16197]
122453073  14-3-3 protein beta/alpha-like [KO:K16197]
122445227  14-3-3 protein theta-like [KO:K16197]
122447849  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
122433054  YWHAG; 14-3-3 protein gamma [KO:K16198]
122420551  YWHAH; 14-3-3 protein eta [KO:K16198]
122445589  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
122425067  CTNNB1; catenin beta-1 [KO:K02105]
122439955  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
122442941  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
122433487  AXIN1; axin-1 isoform X1 [KO:K02157]
122425340  AXIN2; axin-2 isoform X1 [KO:K04385]
122420337  NKD1; protein naked cuticle homolog 1 [KO:K03213]
122454451  NKD2; protein naked cuticle homolog 2 isoform X1 [KO:K03213]
122439921  TCF7; transcription factor 7 isoform X1 [KO:K02620]
122441729  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
122445909  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
122422034  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
122451212  MYC; myc proto-oncogene protein [KO:K04377]
122430666  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
122424006  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
122429373  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
122444890  SOX2; transcription factor SOX-2 [KO:K16796]
122451008  SNAI2; zinc finger protein SNAI2 [KO:K05706]
122449723  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
122449787  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
122438358  ACTG1; actin, cytoplasmic 2 [KO:K05692]
122432952  ACTB; actin, cytoplasmic 1 [KO:K05692]
122439856  CTNNA1; catenin alpha-1 [KO:K05691]
122441796  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
122446497  CTNNA3; catenin alpha-3 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
ccad04120  Ubiquitin mediated proteolysis
ccad04310  Wnt signaling pathway
ccad04350  TGF-beta signaling pathway
ccad04520  Adherens junction
ccad04530  Tight junction
KO pathway
ko04390   
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