KEGG   PATHWAY: mcal04390
Entry
mcal04390                   Pathway                                
Name
Hippo signaling pathway - Mus caroli (Ryukyu mouse)
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
mcal04390  Hippo signaling pathway
mcal04390

Other DBs
GO: 0035329
Organism
Mus caroli (Ryukyu mouse) [GN:mcal]
Gene
110300625  Crb1; protein crumbs homolog 1 isoform X1 [KO:K16681]
110289430  Crb2; protein crumbs homolog 2 [KO:K16681]
110300435  Pard3; partitioning defective 3 homolog isoform X7 [KO:K04237]
110287295  Pard6b; partitioning defective 6 homolog beta [KO:K06093]
110299798  Pard6a; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
110284823  Pard6g; partitioning defective 6 homolog gamma isoform X1 [KO:K06093]
110292460  Prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
110290944  Prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
110292253  Patj; inaD-like protein isoform X1 [KO:K06092]
110306904  Mpp5; MAGUK p55 subfamily member 5 isoform X1 [KO:K06091]
110286729  Amot; angiomotin isoform X1 [KO:K16819]
110301372  Yap1; transcriptional coactivator YAP1 isoform X2 [KO:K16687]
110291173  Wwtr1; WW domain-containing transcription regulator protein 1 isoform X1 [KO:K16820]
110300286  Cdh1; cadherin-1 [KO:K05689]
110309336  Ajuba; LIM domain-containing protein ajuba [KO:K16682]
110298965  Wtip; Wilms tumor protein 1-interacting protein [KO:K16682]
110301579  Limd1; LIM domain-containing protein 1 [KO:K16682]
110306166  Nf2; merlin isoform X1 [KO:K16684]
110305066  Wwc1; protein KIBRA [KO:K16685]
110307131  Frmd6; FERM domain-containing protein 6 isoform X2 [KO:K16822]
110306679  Sav1; protein salvador homolog 1 [KO:K16686]
110310568  Stk3; serine/threonine-protein kinase 3 isoform X1 [KO:K04412]
110294836  Rassf6; ras association domain-containing protein 6 isoform X1 [KO:K09854]
110301468  Rassf1; ras association domain-containing protein 1 isoform X2 [KO:K09850]
110305092  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
110299736  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
110302129  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
110312643  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
110298725  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
110309355  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
110284493  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X2 [KO:K04354]
110294530  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma isoform X3 [KO:K04354]
110303798  Lats1; serine/threonine-protein kinase LATS1 isoform X1 [KO:K08791] [EC:2.7.11.1]
110309825  Lats2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
110296257  Mob1a; MOB kinase activator 1A isoform X1 [KO:K06685]
110294184  Mob1b; MOB kinase activator 1B [KO:K06685]
110285541  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
110294013  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
110294931  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
110288037  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
110294927  Tp53bp2; apoptosis-stimulating of p53 protein 2 [KO:K16823]
110305811  Llgl1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
110304844  Llgl2; lethal(2) giant larvae protein homolog 2 isoform X1 [KO:K06094]
110310223  Scrib; protein scribble homolog isoform X1 [KO:K16175]
110311707  Dlg1; disks large homolog 1 isoform X4 [KO:K12076]
110299456  Dlg2; disks large homolog 2 isoform X6 [KO:K12075]
110302744  disks large homolog 2-like [KO:K12075]
110286480  Dlg3; disks large homolog 3 isoform X1 [KO:K21098]
110304162  Dlg4; disks large homolog 4 isoform X7 [KO:K11828]
110309203  Dlg5; disks large homolog 5 isoform X2 [KO:K24050]
110306106  Csnk1d; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
110310208  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
110285422  Btrc; F-box/WD repeat-containing protein 1A isoform X8 [KO:K03362]
110304634  Fbxw11; F-box/WD repeat-containing protein 11 isoform X5 [KO:K03362]
110292302  Tp73; tumor protein p73 isoform X1 [KO:K10148]
110297909  Bbc3; bcl-2-binding component 3 isoform X1 [KO:K10132]
110283997  Tead3; transcriptional enhancer factor TEF-5 [KO:K09448]
110298119  Tead2; transcriptional enhancer factor TEF-4 [KO:K09448]
110297779  Tead1; transcriptional enhancer factor TEF-1 isoform X5 [KO:K09448]
110296037  Tead4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
110303217  Ccn2; CCN family member 2 [KO:K06827]
110297010  Gli2; zinc finger protein GLI2 [KO:K16798]
110295417  Areg; amphiregulin [KO:K09782]
110305684  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
110294614  Afp; alpha-fetoprotein [KO:K16144]
110311769  integrin beta-2-like protein [KO:K06464]
110303281  Itgb2; integrin beta-2 [KO:K06464]
110284837  Fgf1; fibroblast growth factor 1 isoform X1 [KO:K18496]
110298438  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
110292955  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
110306834  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
110292408  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
110301725  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
110284722  Smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
110284497  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
110301346  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
110284933  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
110289488  Bmp2; bone morphogenetic protein 2 [KO:K21283]
110309274  Bmp4; bone morphogenetic protein 4 [KO:K04662]
110301679  Bmp5; bone morphogenetic protein 5 [KO:K04663]
110307798  Bmp6; bone morphogenetic protein 6 [KO:K16620]
110283962  Bmp7; bone morphogenetic protein 7 [KO:K16621]
110293403  bone morphogenetic protein 8A [KO:K16622]
110292195  bone morphogenetic protein 8B [KO:K16622]
110289974  Gdf5; growth/differentiation factor 5 [KO:K04664]
110293753  Gdf6; growth/differentiation factor 6 [KO:K20012]
110306402  Gdf7; growth/differentiation factor 7 isoform X1 [KO:K20013]
110303725  Amh; muellerian-inhibiting factor [KO:K04665]
110309158  Bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
110290823  Bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
110291041  Bmpr2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
110299753  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
110289711  Id1; DNA-binding protein inhibitor ID-1 isoform X1 [KO:K04680]
110306918  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
110310964  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
110296313  Wnt2; protein Wnt-2 [KO:K00182]
110291476  Wnt2b; protein Wnt-2b [KO:K00182]
110305853  Wnt3a; protein Wnt-3a [KO:K00312]
110304911  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
110293218  Wnt4; protein Wnt-4 isoform X1 [KO:K00408]
110295760  Wnt5b; protein Wnt-5b [KO:K00444]
110309360  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
110299810  Wnt6; protein Wnt-6 [KO:K00445]
110310689  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
110296669  Wnt7a; protein Wnt-7a isoform X1 [KO:K00572]
110285759  Wnt8b; protein Wnt-8b [KO:K00714]
110285093  Wnt8a; protein Wnt-8a [KO:K00714]
110306039  Wnt9a; protein Wnt-9a [KO:K01064]
110305968  Wnt9b; protein Wnt-9b [KO:K01064]
110310912  Wnt10b; protein Wnt-10b isoform X1 [KO:K01357]
110300434  Wnt10a; protein Wnt-10a [KO:K01357]
110298907  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
110296883  Wnt16; protein Wnt-16 [KO:K01558]
110301431  Fzd7; frizzled-7 [KO:K02432]
110294363  Fzd1; frizzled-1 [KO:K02432]
110305336  Fzd2; frizzled-2 [KO:K02235]
110309352  Fzd3; frizzled-3 [KO:K02329]
110298417  Fzd4; frizzled-4 [KO:K02354]
110294401  Fzd5; frizzled-5 [KO:K02375]
110284745  Fzd8; frizzled-8 [KO:K02375]
110310580  Fzd6; frizzled-6 [KO:K02376]
110295350  Fzd9; frizzled-9 [KO:K02842]
110295197  Fzd10; frizzled-10 [KO:K02842]
110292264  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
110304161  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
110311604  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
110310210  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
110306902  Ywhaq; 14-3-3 protein theta [KO:K16197]
110312563  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
110305021  Ywhae; 14-3-3 protein epsilon [KO:K06630]
110294181  Ywhah; 14-3-3 protein eta [KO:K16198]
110294960  Ywhag; 14-3-3 protein gamma [KO:K16198]
110288882  14-3-3 protein eta [KO:K16198]
110311365  Gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
110301052  Ctnnb1; catenin beta-1 [KO:K02105]
110284455  Apc; adenomatous polyposis coli protein isoform X4 [KO:K02085]
110303367  Apc2; adenomatous polyposis coli protein 2 isoform X2 [KO:K02085]
110284040  Axin1; axin-1 isoform X1 [KO:K02157]
110304669  Axin2; axin-2 [KO:K04385]
110308227  Nkd2; protein naked cuticle homolog 2 isoform X1 [KO:K03213]
110300047  Nkd1; protein naked cuticle homolog 1 [KO:K03213]
110304948  Tcf7; transcription factor 7 isoform X2 [KO:K02620]
110296038  Tcf7l1; transcription factor 7-like 1 isoform X2 [KO:K04490]
110285273  Tcf7l2; transcription factor 7-like 2 isoform X5 [KO:K04491]
110290892  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
110310583  Myc; myc proto-oncogene protein [KO:K04377]
110298189  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
110296334  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
110312516  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
110291405  Sox2; transcription factor SOX-2 [KO:K16796]
110311690  Snai2; zinc finger protein SNAI2 [KO:K05706]
110302303  baculoviral IAP repeat-containing protein 3 [KO:K16060]
110301861  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
110304283  Actg1; actin, cytoplasmic 2 [KO:K05692]
110295381  Actb; actin, cytoplasmic 1 [KO:K05692]
110302662  Ctnna3; catenin alpha-3 isoform X1 [KO:K05691]
110284850  Ctnna1; catenin alpha-1 isoform X1 [KO:K05691]
110295850  Ctnna2; 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
mcal04120  Ubiquitin mediated proteolysis
mcal04310  Wnt signaling pathway
mcal04350  TGF-beta signaling pathway
mcal04520  Adherens junction
mcal04530  Tight junction
KO pathway
ko04390   
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