KEGG   PATHWAY: mna04390
Entry
mna04390                    Pathway                                
Name
Hippo signaling pathway - Miniopterus natalensis (Natal long-fingered bat)
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
mna04390  Hippo signaling pathway
mna04390

Other DBs
GO: 0035329
Organism
Miniopterus natalensis (Natal long-fingered bat) [GN:mna]
Gene
107535565  CRB2; protein crumbs homolog 2 [KO:K16681]
107525082  PARD3; partitioning defective 3 homolog [KO:K04237]
107541559  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
107538237  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
107542884  PARD6A; partitioning defective 6 homolog alpha [KO:K06093]
107540144  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
107529541  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
107531752  PATJ; inaD-like protein [KO:K06092]
107545672  MPP5; MAGUK p55 subfamily member 5 isoform X1 [KO:K06091]
107525794  AMOT; angiomotin [KO:K16819]
107532419  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
107543852  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
107527895  CDH1; cadherin-1 [KO:K05689]
107531696  AJUBA; LIM domain-containing protein ajuba isoform X1 [KO:K16682]
107543501  WTIP; Wilms tumor protein 1-interacting protein isoform X1 [KO:K16682]
107524257  LIMD1; LIM domain-containing protein 1 [KO:K16682]
107526198  NF2; merlin isoform X1 [KO:K16684]
107537894  WWC1; protein KIBRA [KO:K16685]
107537008  FRMD1; FERM domain-containing protein 1 [KO:K16821]
107525866  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
107525860  SAV1; protein salvador homolog 1 [KO:K16686]
107526150  STK3; serine/threonine-protein kinase 3 [KO:K04412]
107534502  RASSF6; ras association domain-containing protein 6 [KO:K09854]
107545083  ras association domain-containing protein 1-like [KO:K09850]
107525394  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107534103  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
107540441  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
107531299  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
107524098  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
107529884  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
107530370  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
107529477  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
107529951  LATS2; serine/threonine-protein kinase LATS2 isoform X1 [KO:K08791] [EC:2.7.11.1]
107545758  LATS1; serine/threonine-protein kinase LATS1 isoform X1 [KO:K08791] [EC:2.7.11.1]
107529264  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
107532651  MOB1B; MOB kinase activator 1B [KO:K06685]
107534692  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
107533957  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
107529564  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
107543610  TP53BP2; apoptosis-stimulating of p53 protein 2 [KO:K16823]
107536644  LLGL2; lethal(2) giant larvae protein homolog 2 [KO:K06094]
107524532  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
107544221  SCRIB; protein scribble homolog isoform X1 [KO:K16175]
107527282  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
107532464  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
107532901  DLG3; disks large homolog 3 isoform X1 [KO:K21098]
107544252  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
107539997  DLG5; disks large homolog 5 isoform X1 [KO:K24050]
107539077  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
107544538  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
107535702  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
107542570  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
107537496  TP73; tumor protein p73 [KO:K10148]
107540044  BBC3; bcl-2-binding component 3 [KO:K10132]
107538864  TEAD4; transcriptional enhancer factor TEF-3 [KO:K09448]
107545571  TEAD3; transcriptional enhancer factor TEF-5 [KO:K09448]
107535315  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
107531890  TEAD2; transcriptional enhancer factor TEF-4 isoform X1 [KO:K09448]
107530932  CTGF; connective tissue growth factor [KO:K06827]
107543207  GLI2; zinc finger protein GLI2 [KO:K16798]
107534488  AREG; amphiregulin [KO:K09782]
107532046  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
107534484  AFP; alpha-fetoprotein [KO:K16144]
107534485  alpha-fetoprotein-like [KO:K16144]
107543669  ITGB2; integrin beta-2 [KO:K06464]
107531500  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
107534176  TGFB1; transforming growth factor beta-1 [KO:K13375]
107543622  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
107533843  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
107544970  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
107526381  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
107546624  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
107546622  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
107525935  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
107546640  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
107526505  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
107536373  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
107525879  BMP4; bone morphogenetic protein 4 [KO:K04662]
107525808  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
107529113  BMP6; bone morphogenetic protein 6 [KO:K16620]
107529673  BMP7; bone morphogenetic protein 7 [KO:K16621]
107541712  BMP8A; LOW QUALITY PROTEIN: bone morphogenetic protein 8A [KO:K16622]
107537217  GDF5; growth/differentiation factor 5 [KO:K04664]
107534547  AMH; muellerian-inhibiting factor [KO:K04665]
107538481  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
107531931  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
107533955  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
107532516  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
107527734  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
107526675  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
107528239  WNT1; proto-oncogene Wnt-1 [KO:K03209]
107545293  WNT2B; protein Wnt-2b [KO:K00182]
107524863  WNT2; protein Wnt-2 [KO:K00182]
107529919  WNT3A; protein Wnt-3a [KO:K00312]
107530219  WNT3; proto-oncogene Wnt-3 [KO:K00312]
107538446  WNT4; protein Wnt-4 [KO:K00408]
107546464  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
107530635  WNT5A; protein Wnt-5a [KO:K00444]
107524769  WNT6; protein Wnt-6 [KO:K00445]
107537987  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
107534839  WNT7B; protein Wnt-7b [KO:K00572]
107542524  WNT8B; protein Wnt-8b [KO:K00714]
107530103  WNT8A; protein Wnt-8a [KO:K00714]
107529865  WNT9A; protein Wnt-9a [KO:K01064]
107530990  WNT9B; protein Wnt-9b [KO:K01064]
107528238  WNT10B; protein Wnt-10b [KO:K01357]
107524821  WNT10A; protein Wnt-10a [KO:K01357]
107524451  WNT11; protein Wnt-11 [KO:K01384]
107537386  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
107541653  FZD1; frizzled-1 [KO:K02432]
107533927  FZD7; frizzled-7 [KO:K02432]
107528834  FZD2; frizzled-2 [KO:K02235]
107537768  FZD3; frizzled-3 isoform X1 [KO:K02329]
107532452  FZD4; frizzled-4 isoform X1 [KO:K02354]
107525076  FZD8; frizzled-8 [KO:K02375]
107524716  FZD5; frizzled-5 [KO:K02375]
107546030  FZD6; frizzled-6 isoform X1 [KO:K02376]
107526557  FZD9; frizzled-9 [KO:K02842]
107529641  FZD10; frizzled-10 [KO:K02842]
107541116  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
107543696  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
107544485  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
107530918  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
107526642  YWHAQ; 14-3-3 protein theta [KO:K16197]
107526139  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
107535607  YWHAE; 14-3-3 protein epsilon [KO:K06630]
107526525  YWHAG; 14-3-3 protein gamma [KO:K16198]
107526222  YWHAH; 14-3-3 protein eta [KO:K16198]
107527219  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107524266  CTNNB1; catenin beta-1 [KO:K02105]
107546495  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
107534581  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
107539654  AXIN1; axin-1 isoform X1 [KO:K02157]
107538303  AXIN2; axin-2 isoform X1 [KO:K04385]
107536691  NKD2; protein naked cuticle homolog 2 [KO:K03213]
107525397  TCF7; transcription factor 7 isoform X1 [KO:K02620]
107528616  TCF7L1; transcription factor 7-like 1 [KO:K04490]
107536455  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
107538292  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
107539494  MYC; myc proto-oncogene protein [KO:K04377]
107537434  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
107538904  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
107536896  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
107541087  SOX2; transcription factor SOX-2 [KO:K16796]
107526455  SNAI2; zinc finger protein SNAI2 [KO:K05706]
107532417  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
107532418  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
107539076  ACTG1; actin, cytoplasmic 2 [KO:K05692]
107537600  ACTB; actin, cytoplasmic 1 [KO:K05692]
107529240  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
107526073  catenin alpha-3 [KO:K05691]
107530128  CTNNA1; catenin alpha-1 [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
mna04120  Ubiquitin mediated proteolysis
mna04310  Wnt signaling pathway
mna04350  TGF-beta signaling pathway
mna04520  Adherens junction
mna04530  Tight junction
KO pathway
ko04390   
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