KEGG   PATHWAY: ko04390Help
Entry
ko04390                     Pathway                                

Name
Hippo signaling pathway
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
09130 Environmental Information Processing; 09132 Signal transduction
BRITE hierarchy
Pathway map
ko04390  Hippo signaling pathway
ko04390

Ortholog table
Module
M00679  BMP signaling [PATH:ko04390]
M00680  TGF-beta signaling [PATH:ko04390]
M00683  Hippo signaling [PATH:ko04390]
Disease
H00800  Loeys-Dietz syndrome (LDS)
H01385  Rienhoff syndrome
H01438  Neurofibromatosis type 2
Other DBs
BSID: 750388
GO: 0035329
Orthology
K16681  protein crumbs
K04237  partitioning defective protein 3
K06093  partitioning defective protein 6
K18952  atypical protein kinase C zeta type [EC:2.7.11.13]
K06069  atypical protein kinase C iota type [EC:2.7.11.13]
K06092  InaD-like protein
K06091  MAGUK p55 subfamily member 5
K16819  angiomotin
K16687  transcriptional coactivator YAP1
K16820  WW domain-containing transcription regulator protein 1
K05689  cadherin 1, type 1, E-cadherin
K16682  LIM domain-containing protein
K16684  merlin
K16685  protein KIBRA
K16821  FERM domain-containing protein 1
K16822  FERM domain-containing protein 6
K16686  scaffold protein salvador
K04412  serine/threonine kinase 3
K09854  Ras association domain-containing protein 6
K09850  Ras association domain-containing protein 1
K04382  serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K03456  serine/threonine-protein phosphatase 2A regulatory subunit A
K04354  serine/threonine-protein phosphatase 2A regulatory subunit B
K08791  serine/threonine-protein kinase LATS1/2 [EC:2.7.11.1]
K06685  MOB kinase activator 1
K06269  serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K16823  apoptosis-stimulating of p53 protein 2
K06094  lethal(2) giant larvae protein
K16175  protein scribble
K12076  disks large protein 1
K11828  discs large protein 4
K12075  discs large protein 2
K21098  discs large protein 3
K08959  casein kinase 1, delta [EC:2.7.11.1]
K08960  casein kinase 1, epsilon [EC:2.7.11.1]
K03362  F-box and WD-40 domain protein 1/11
K10148  tumor protein p73
K10132  Bcl-2-binding component 3
K09448  transcriptional enhancer factor
K06827  connective tissue growth factor
K16798  zinc finger protein GLI2
K09782  amphiregulin
K08731  baculoviral IAP repeat-containing protein 5
K16144  alpha-fetoprotein
K06464  integrin beta 2
K18496  fibroblast growth factor 1
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K04674  TGF-beta receptor type-1 [EC:2.7.11.30]
K04388  TGF-beta receptor type-2 [EC:2.7.11.30]
K19631  mothers against decapentaplegic homolog 7
K04500  mothers against decapentaplegic homolog 2/3
K04501  mothers against decapentaplegic homolog 4
K03982  plasminogen activator inhibitor 1
K21283  bone morphogenetic protein 2
K04662  bone morphogenetic protein 4
K04663  bone morphogenetic protein 5
K16620  bone morphogenetic protein 6
K16621  bone morphogenetic protein 7
K16622  bone morphogenetic protein 8
K04664  growth differentiation factor 5
K20012  growth differentiation factor 6
K20013  growth differentiation factor 7
K04665  anti-mullerian hormone
K04673  bone morphogenetic protein receptor type-1A [EC:2.7.11.30]
K13578  bone morphogenetic protein receptor type-1B [EC:2.7.11.30]
K04671  bone morphogenetic protein receptor type-2 [EC:2.7.11.30]
K04676  mothers against decapentaplegic homolog 1
K04680  DNA-binding protein inhibitor ID1
K17693  DNA-binding protein inhibitor ID2
K03209  wingless-type MMTV integration site family, member 1
K00182  wingless-type MMTV integration site family, member 2
K00312  wingless-type MMTV integration site family, member 3
K00408  wingless-type MMTV integration site family, member 4
K00444  wingless-type MMTV integration site family, member 5
K00445  wingless-type MMTV integration site family, member 6
K00572  wingless-type MMTV integration site family, member 7
K00714  wingless-type MMTV integration site family, member 8
K01064  wingless-type MMTV integration site family, member 9
K01357  wingless-type MMTV integration site family, member 10
K01384  wingless-type MMTV integration site family, member 11
K01558  wingless-type MMTV integration site family, member 16
K02432  frizzled 1/7
K02235  frizzled 2
K02329  frizzled 3
K02354  frizzled 4
K02375  frizzled 5/8
K02376  frizzled 6
K02842  frizzled 9/10
K02353  segment polarity protein dishevelled
K16197  14-3-3 protein beta/theta/zeta
K06630  14-3-3 protein epsilon
K16198  14-3-3 protein gamma/eta
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K02105  catenin beta 1
K02085  adenomatosis polyposis coli protein
K02157  axin 1
K04385  axin 2
K02620  transcription factor 7
K04490  transcription factor 7-like 1
K04491  transcription factor 7-like 2
K04492  lymphoid enhancer-binding factor 1
K04377  Myc proto-oncogene protein
K04503  G1/S-specific cyclin-D1
K10151  G1/S-specific cyclin-D2
K10152  G1/S-specific cyclin-D3
K16796  transcription factor SOX2 (SOX group B)
K05706  snail 2
K05692  actin beta/gamma 1
K05691  catenin alpha
Reference
  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
  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
  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
  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
  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
  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
  Authors
Halder G, Johnson RL
  Title
Hippo signaling: growth control and beyond.
  Journal
Development 138:9-22 (2011)
DOI:10.1242/dev.045500
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
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