KEGG   PATHWAY: ccan04390
Entry
ccan04390                   Pathway                                
Name
Hippo signaling pathway - Castor canadensis (American beaver)
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
ccan04390  Hippo signaling pathway
ccan04390

Other DBs
GO: 0035329
Organism
Castor canadensis (American beaver) [GN:ccan]
Gene
109679531  Crb2; protein crumbs homolog 2 [KO:K16681]
109684712  partitioning defective 3 homolog isoform X1 [KO:K04237]
109684714  partitioning defective 3 homolog [KO:K04237]
109687131  Pard6g; partitioning defective 6 homolog gamma [KO:K06093]
109693692  Pard6b; LOW QUALITY PROTEIN: partitioning defective 6 homolog beta [KO:K06093]
109691271  Pard6a; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
109691439  Prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
109700210  Prkci; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
109703001  LOW QUALITY PROTEIN: inaD-like protein [KO:K06092]
109699478  Mpp5; MAGUK p55 subfamily member 5 isoform X1 [KO:K06091]
109689099  Yap1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
109681529  WW domain-containing transcription regulator protein 1 [KO:K16820]
109693763  Cdh1; cadherin-1 isoform X1 [KO:K05689]
109685809  LIM domain-containing protein ajuba-like [KO:K16682]
109684888  Limd1; LIM domain-containing protein 1 [KO:K16682]
109685801  LIM domain-containing protein ajuba [KO:K16682]
109697016  Wtip; LOW QUALITY PROTEIN: Wilms tumor protein 1-interacting protein [KO:K16682]
109684885  LIM domain-containing protein 1-like [KO:K16682]
109681639  Nf2; merlin isoform X1 [KO:K16684]
109681608  Wwc1; protein KIBRA [KO:K16685]
109688991  Frmd1; LOW QUALITY PROTEIN: FERM domain-containing protein 1 [KO:K16821]
109696452  Frmd6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
109687220  Sav1; protein salvador homolog 1 isoform X1 [KO:K16686]
109688653  Stk3; LOW QUALITY PROTEIN: serine/threonine-protein kinase 3 [KO:K04412]
109693231  Rassf1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
109692163  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
109689490  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
109687790  Ppp2r1b; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
109699358  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
109694061  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
109687460  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
109698633  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
109684624  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
109694196  Lats1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
109689019  Lats2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
109688144  Mob1a; MOB kinase activator 1A isoform X1 [KO:K06685]
109679521  MOB kinase activator 1B [KO:K06685]
109679334  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
109688628  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
109685544  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
109677048  Tp53bp2; apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
109681511  Llgl2; lethal(2) giant larvae protein homolog 2 [KO:K06094]
109683618  Llgl1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
109690802  Scrib; protein scribble homolog isoform X1 [KO:K16175]
109699995  disks large homolog 1 [KO:K12076]
109678843  disks large homolog 2 [KO:K12075]
109678844  disks large homolog 2-like [KO:K12075]
109680747  Dlg3; disks large homolog 3 isoform X1 [KO:K21098]
109674497  Dlg4; disks large homolog 4 isoform X1 [KO:K11828]
109682235  Dlg5; disks large homolog 5 isoform X1 [KO:K24050]
109703071  Csnk1d; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
109692849  casein kinase I [KO:K08960] [EC:2.7.11.1]
109696980  Fbxw11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
109691321  Btrc; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
109682848  Tp73; tumor protein p73 isoform X1 [KO:K10148]
109697533  Bbc3; bcl-2-binding component 3 isoform X1 [KO:K10132]
109689863  Tead3; transcriptional enhancer factor TEF-5 [KO:K09448]
109699739  Tead1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
109683893  Tead2; transcriptional enhancer factor TEF-4 [KO:K09448]
109698242  Tead4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
109684563  Ctgf; connective tissue growth factor [KO:K06827]
109693799  Gli2; zinc finger protein GLI2 [KO:K16798]
109681114  Areg; amphiregulin [KO:K09782]
109683144  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
109678589  Afp; alpha-fetoprotein [KO:K16144]
109678592  alpha-fetoprotein-like [KO:K16144]
109702039  integrin beta-2-like [KO:K06464]
109694990  Itgb2; integrin beta-2 isoform X1 [KO:K06464]
109684968  Fgf1; fibroblast growth factor 1 [KO:K18496]
109684969  fibroblast growth factor 1-like [KO:K18496]
109685632  Tgfb1; transforming growth factor beta-1 [KO:K13375]
109698650  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
109686152  Tgfb3; transforming growth factor beta-3 [KO:K13377]
109691424  Tgfbr1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
109681522  Tgfbr2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
109683625  Smad7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
109700302  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 2-like [KO:K04500]
109701514  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
109687032  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
109692813  Serpine1; plasminogen activator inhibitor 1 [KO:K03982]
109677386  Bmp2; bone morphogenetic protein 2 [KO:K21283]
109701382  Bmp4; bone morphogenetic protein 4 [KO:K04662]
109677097  Bmp5; LOW QUALITY PROTEIN: bone morphogenetic protein 5 [KO:K04663]
109692215  Bmp6; bone morphogenetic protein 6 [KO:K16620]
109690684  Bmp7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
109697321  bone morphogenetic protein 8B-like isoform X1 [KO:K16622]
109691571  bone morphogenetic protein 8B isoform X1 [KO:K16622]
109681889  Gdf5; growth/differentiation factor 5 [KO:K04664]
109677714  Gdf6; growth/differentiation factor 6 [KO:K20012]
109681734  Gdf7; growth/differentiation factor 7 isoform X1 [KO:K20013]
109689925  Amh; muellerian-inhibiting factor [KO:K04665]
109684779  Bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
109703066  Bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
109683698  Bmpr2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
109688892  mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
109691793  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
109700135  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
109694825  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
109684416  Wnt2; protein Wnt-2 [KO:K00182]
109681721  Wnt2b; protein Wnt-2b [KO:K00182]
109684805  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
109677070  Wnt3a; protein Wnt-3a [KO:K00312]
109694918  Wnt4; protein Wnt-4 [KO:K00408]
109683366  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
109683371  Wnt5b; protein Wnt-5b [KO:K00444]
109693790  Wnt6; protein Wnt-6 [KO:K00445]
109679085  protein Wnt-7a-like [KO:K00572]
109699751  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
109700179  Wnt8a; protein Wnt-8a [KO:K00714]
109698141  Wnt8b; protein Wnt-8b [KO:K00714]
109700763  Wnt9a; protein Wnt-9a [KO:K01064]
109702078  Wnt9b; protein Wnt-9b [KO:K01064]
109694821  Wnt10b; protein Wnt-10b [KO:K01357]
109693094  Wnt10a; protein Wnt-10a [KO:K01357]
109698403  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
109685536  Wnt16; protein Wnt-16 [KO:K01558]
109683768  Fzd7; frizzled-7 [KO:K02432]
109677487  Fzd1; frizzled-1 [KO:K02432]
109686522  Fzd2; frizzled-2 [KO:K02235]
109695813  Fzd3; frizzled-3 [KO:K02329]
109695029  Fzd4; frizzled-4 [KO:K02354]
109692648  Fzd5; frizzled-5 [KO:K02375]
109700329  Fzd8; frizzled-8 [KO:K02375]
109694264  Fzd6; frizzled-6 [KO:K02376]
109695912  Fzd10; frizzled-10 [KO:K02842]
109702389  Fzd9; LOW QUALITY PROTEIN: frizzled-9 [KO:K02842]
109674455  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
109681149  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
109694105  Dvl3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
109681358  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
109695924  Ywhaq; 14-3-3 protein theta [KO:K16197]
109697135  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
109682601  Ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
109681582  Ywhag; 14-3-3 protein gamma [KO:K16198]
109700917  Ywhah; 14-3-3 protein eta [KO:K16198]
109685333  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
109689873  Ctnnb1; catenin beta-1 [KO:K02105]
109691007  Apc2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
109699342  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
109694685  Axin1; axin-1 isoform X1 [KO:K02157]
109681311  Axin2; axin-2 [KO:K04385]
109698370  Nkd1; protein naked cuticle homolog 1 [KO:K03213]
109702116  Nkd2; protein naked cuticle homolog 2 isoform X1 [KO:K03213]
109689465  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
109686184  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
109688561  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
109688935  lymphoid enhancer-binding factor 1 [KO:K04492]
109699943  Myc; myc proto-oncogene protein [KO:K04377]
109696351  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
109688460  G1/S-specific cyclin-D2-like [KO:K10151]
109688461  G1/S-specific cyclin-D2 [KO:K10151]
109682157  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
109699101  Sox2; transcription factor SOX-2 [KO:K16796]
109677704  Snai2; zinc finger protein SNAI2 [KO:K05706]
109689097  Birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
109689098  Birc3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
109700700  actin, cytoplasmic 1 isoform X1 [KO:K05692]
109678026  catenin alpha-2 [KO:K05691]
109681367  Ctnna1; catenin alpha-1 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
ccan04120  Ubiquitin mediated proteolysis
ccan04310  Wnt signaling pathway
ccan04350  TGF-beta signaling pathway
ccan04520  Adherens junction
ccan04530  Tight junction
KO pathway
ko04390   
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