KEGG   PATHWAY: hgl04390
Entry
hgl04390                    Pathway                                
Name
Hippo signaling pathway - Heterocephalus glaber (naked mole-rat)
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
hgl04390  Hippo signaling pathway
hgl04390

Other DBs
GO: 0035329
Organism
Heterocephalus glaber (naked mole-rat) [GN:hgl]
Gene
101696315  Wnt5b; Wnt family member 5B [KO:K00444]
101696976  Gdf5; growth differentiation factor 5 [KO:K04664]
101697210  Fzd1; frizzled class receptor 1 [KO:K02432]
101697238  Fzd3; frizzled class receptor 3 [KO:K02329]
101697279  Prkci; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
101697582  Wnt11; Wnt family member 11 [KO:K01384]
101697659  Gli2; GLI family zinc finger 2 [KO:K16798]
101698044  Ppp1cb; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
101698823  Wnt6; Wnt family member 6 [KO:K00445]
101698973  Llgl1; LLGL1, scribble cell polarity complex component [KO:K06094]
101699189  Apc2; APC2, WNT signaling pathway regulator [KO:K02085]
101699303  Prkcz; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
101699309  Wnt10a; Wnt family member 10A [KO:K01357]
101699461  Yap1; Yes associated protein 1 [KO:K16687]
101699485  Limd1; LIM domains containing 1 [KO:K16682]
101699909  Tcf7l1; transcription factor 7 like 1 [KO:K04490]
101700404  Fzd4; frizzled class receptor 4 [KO:K02354]
101700573  Ppp2r2b; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
101700795  Axin1; axin 1 [KO:K02157]
101700802  Areg; amphiregulin [KO:K09782]
101700899  Bmpr1a; bone morphogenetic protein receptor type 1A [KO:K04673] [EC:2.7.11.30]
101701138  Bmpr2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
101701301  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
101701576  Csnk1d; casein kinase 1 delta [KO:K08959] [EC:2.7.11.1]
101701972  Wnt4; Wnt family member 4 [KO:K00408]
101702483  Actg1; actin gamma 1 [KO:K05692]
101703201  Birc5; baculoviral IAP repeat containing 5 [KO:K08731]
101703470  Ppp2r1a; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
101703764  Smad4; SMAD family member 4 [KO:K04501]
101703903  Serpine1; serpin family E member 1 [KO:K03982]
101703921  Itgb2; integrin subunit beta 2 [KO:K06464]
101704055  Apc; APC, WNT signaling pathway regulator [KO:K02085]
101704230  Tgfb1; transforming growth factor beta 1 [KO:K13375]
101704351  Fzd7; frizzled class receptor 7 [KO:K02432]
101704397  Tgfbr2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
101704740  Myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
101704935  Wnt2b; Wnt family member 2B [KO:K00182]
101705010  Dlg5; discs large MAGUK scaffold protein 5 [KO:K24050]
101705060  Lats2; large tumor suppressor kinase 2 [KO:K08791] [EC:2.7.11.1]
101705080  Ywhab; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
101705408  Ppp1ca; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
101705646  Wnt9b; Wnt family member 9B [KO:K01064]
101705735  Pard3; par-3 family cell polarity regulator [KO:K04237]
101705761  Tead2; TEA domain transcription factor 2 [KO:K09448]
101706100  Nf2; neurofibromin 2 [KO:K16684]
101706196  Bmp7; bone morphogenetic protein 7 [KO:K16621]
101706344  Mob1a; MOB kinase activator 1A [KO:K06685]
101706438  Amot; angiomotin [KO:K16819]
101706835  Ctgf; connective tissue growth factor [KO:K06827]
101706999  Gdf6; growth differentiation factor 6 [KO:K20012]
101707435  Pard6a; par-6 family cell polarity regulator alpha [KO:K06093]
101707457  Tgfb2; transforming growth factor beta 2 [KO:K13376]
101707462  Bmp6; bone morphogenetic protein 6 [KO:K16620]
101707511  Ppp2ca; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
101707810  Tead3; TEA domain transcription factor 3 [KO:K09448]
101707882  Tcf7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
101708062  Ccnd3; cyclin D3 [KO:K10152]
101708071  Id2; inhibitor of DNA binding 2, HLH protein [KO:K17693]
101708098  Dlg3; discs large MAGUK scaffold protein 3 [KO:K21098]
101708392  Fzd10; frizzled class receptor 10 [KO:K02842]
101708403  Csnk1e; casein kinase I isoform epsilon [KO:K08960] [EC:2.7.11.1]
101708587  Dlg4; discs large MAGUK scaffold protein 4 [KO:K11828]
101708645  Ppp2r2a; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
101708659  Fzd5; frizzled class receptor 5 [KO:K02375]
101708726  Fzd9; frizzled class receptor 9 [KO:K02842]
101709704  Ywhah; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
101709720  [KO:K04237]
101709789  Ppp2r2d; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
101710196  Bmpr1b; bone morphogenetic protein receptor type 1B [KO:K13578] [EC:2.7.11.30]
101710380  Tcf7l2; transcription factor 7 like 2 [KO:K04491]
101710484  Wnt16; Wnt family member 16 [KO:K01558]
101710629  Dvl2; dishevelled segment polarity protein 2 [KO:K02353]
101710791  Nkd1; naked cuticle homolog 1 [KO:K03213]
101711023  Lef1; lymphoid enhancer binding factor 1 [KO:K04492]
101711091  Scrib; scribbled planar cell polarity protein [KO:K16175]
101711207  Bmp4; bone morphogenetic protein 4 [KO:K04662]
101711272  Wnt5a; Wnt family member 5A [KO:K00444]
101711517  Ppp2r2c; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
101711747  Wnt8a; Wnt family member 8A [KO:K00714]
101711913  [KO:K16622]
101712009  Amh; anti-Mullerian hormone [KO:K04665]
101712115  Fzd8; frizzled class receptor 8 [KO:K02375]
101712252  Dlg2; discs large MAGUK scaffold protein 2 [KO:K12075]
101712621  Ccnd1; cyclin D1 [KO:K04503]
101712650  [KO:K16198]
101712895  Wwc1; WW and C2 domain containing 1 [KO:K16685]
101712904  Tgfb3; transforming growth factor beta 3 [KO:K13377]
101713378  Smad3; SMAD family member 3 [KO:K23605]
101713401  Fzd2; frizzled class receptor 2 [KO:K02235]
101713890  Crb1; crumbs 1, cell polarity complex component [KO:K16681]
101714057  [KO:K16622]
101714203  Smad2; SMAD family member 2 [KO:K04500]
101714468  Ppp1cc; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
101714477  Ctnna2; catenin alpha 2 [KO:K05691]
101714583  Id1; inhibitor of DNA binding 1, HLH protein [KO:K04680]
101714736  Tead4; TEA domain transcription factor 4 [KO:K09448]
101714844  Bbc3; BCL2 binding component 3 [KO:K10132]
101715077  Wnt8b; Wnt family member 8B [KO:K00714]
101715099  Stk3; serine/threonine kinase 3 [KO:K04412]
101715426  Dvl1; dishevelled segment polarity protein 1 [KO:K02353]
101715480  Wnt9a; Wnt family member 9A [KO:K01064]
101715816  Tead1; TEA domain transcription factor 1 [KO:K09448]
101715878  Ctnna1; catenin alpha 1 [KO:K05691]
101716074  Wnt3a; Wnt family member 3A [KO:K00312]
101716409  Dlg1; discs large MAGUK scaffold protein 1 [KO:K12076]
101716439  Ywhag; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
101716466  Tp73; tumor protein p73 [KO:K10148]
101716964  Axin2; axin 2 [KO:K04385]
101716996  Dvl3; dishevelled segment polarity protein 3 [KO:K02353]
101717238  Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
101717255  Actb; actin beta [KO:K05692]
101717470  Snai2; snail family transcriptional repressor 2 [KO:K05706]
101717777  Fgf1; fibroblast growth factor 1 [KO:K18496]
101718090  Tgfbr1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
101718253  Fbxw11; F-box and WD repeat domain containing 11 [KO:K03362]
101718505  Wtip; Wilms tumor 1 interacting protein [KO:K16682]
101718588  Smad7; SMAD family member 7 [KO:K19631]
101718804  Birc2; baculoviral IAP repeat containing 2 [KO:K16060]
101719143  Birc3; baculoviral IAP repeat containing 3 [KO:K16060]
101719449  Patj; PATJ, crumbs cell polarity complex component [KO:K06092]
101719565  Cdh1; cadherin 1 [KO:K05689]
101719759  Frmd6; FERM domain containing 6 [KO:K16822]
101720117  Ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
101720578  Ctnnb1; catenin beta 1 [KO:K02105]
101720764  Tp53bp2; tumor protein p53 binding protein 2 [KO:K16823]
101720841  [KO:K16197]
101721218  Ajuba; ajuba LIM protein [KO:K16682]
101721478  Crb2; crumbs 2, cell polarity complex component [KO:K16681]
101721480  Ccnd2; cyclin D2 [KO:K10151]
101721668  Llgl2; LLGL2, scribble cell polarity complex component [KO:K06094]
101721852  Mob1b; MOB kinase activator 1B [KO:K06685]
101721954  Ywhaz; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
101722244  Ppp2r1b; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
101722280  Wnt10b; Wnt family member 10B [KO:K01357]
101722552  Fzd6; frizzled class receptor 6 [KO:K02376]
101722616  Gdf7; growth differentiation factor 7 [KO:K20013]
101722636  Wnt1; Wnt family member 1 [KO:K03209]
101722908  Wwtr1; WW domain containing transcription regulator 1 [KO:K16820]
101723191  Pard6g; par-6 family cell polarity regulator gamma [KO:K06093]
101723266  Sox2; SRY-box 2 [KO:K16796]
101723419  Bmp2; bone morphogenetic protein 2 [KO:K21283]
101723565  Wnt2; Wnt family member 2 [KO:K00182]
101723820  Bmp5; bone morphogenetic protein 5 [KO:K04663]
101724481  Mpp5; membrane palmitoylated protein 5 [KO:K06091]
101724651  Wnt3; Wnt family member 3 [KO:K00312]
101724835  Rassf6; Ras association domain family member 6 [KO:K09854]
101724837  Pard6b; par-6 family cell polarity regulator beta [KO:K06093]
101724879  Ctnna3; catenin alpha 3 [KO:K05691]
101725200  Lats1; large tumor suppressor kinase 1 [KO:K08791] [EC:2.7.11.1]
101725205  Afp; alpha fetoprotein [KO:K16144]
101725735  Wnt7a; Wnt family member 7A [KO:K00572]
101725771  Nkd2; naked cuticle homolog 2 [KO:K03213]
101725903  Smad1; SMAD family member 1 [KO:K04676]
101726191  Ppp2cb; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
101726616  Wnt7b; Wnt family member 7B [KO:K00572]
101726669  Sav1; salvador family WW domain containing protein 1 [KO:K16686]
101726740  Btrc; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
106010032  [KO:K06069] [EC:2.7.11.13]
106010799  [KO:K06069] [EC:2.7.11.13]
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
hgl04120  Ubiquitin mediated proteolysis
hgl04310  Wnt signaling pathway
hgl04350  TGF-beta signaling pathway
hgl04520  Adherens junction
hgl04530  Tight junction
KO pathway
ko04390   

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