KEGG   PATHWAY: pon04390
Entry
pon04390                    Pathway                                
Name
Hippo signaling pathway - Pongo abelii (Sumatran orangutan)
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
pon04390  Hippo signaling pathway
pon04390

Other DBs
GO: 0035329
Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100448356  CRB1; protein crumbs homolog 1 isoform X1 [KO:K16681]
100459778  CRB2; protein crumbs homolog 2 [KO:K16681]
100431669  PARD3; partitioning defective 3 homolog isoform X3 [KO:K04237]
100446406  PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
100446683  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
112129943  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
100174126  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
100173964  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
100446155  PATJ; inaD-like protein [KO:K06092]
100171889  MPP5; MAGUK p55 subfamily member 5 [KO:K06091]
100439462  AMOT; angiomotin isoform X1 [KO:K16819]
100456879  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
100437619  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
100174439  CDH1; cadherin-1 precursor [KO:K05689]
100438677  AJUBA; LIM domain-containing protein ajuba isoform X1 [KO:K16682]
100449006  WTIP; Wilms tumor protein 1-interacting protein [KO:K16682]
100449715  LIMD1; LIM domain-containing protein 1 [KO:K16682]
100442887  NF2; merlin isoform X1 [KO:K16684]
100171868  WWC1; protein KIBRA isoform X1 [KO:K16685]
100461119  FRMD1; FERM domain-containing protein 1 isoform X1 [KO:K16821]
100438906  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
100435936  SAV1; protein salvador homolog 1 isoform X1 [KO:K16686]
100172589  STK3; serine/threonine-protein kinase 3 [KO:K04412]
100436744  RASSF6; ras association domain-containing protein 6 isoform X1 [KO:K09854]
103888520  RASSF1; ras association domain-containing protein 1 isoform X3 [KO:K09850]
100437405  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100461606  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100173260  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100437928  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100436819  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X2 [KO:K04354]
100443527  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
100174027  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
100462193  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
100445882  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
100455398  LATS1; serine/threonine-protein kinase LATS1 isoform X1 [KO:K08791] [EC:2.7.11.1]
100172677  MOB1A; MOB kinase activator 1A [KO:K06685]
103890436  MOB1B; MOB kinase activator 1B isoform X1 [KO:K06685]
100173410  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100459799  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100458223  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100445132  TP53BP2; apoptosis-stimulating of p53 protein 2 [KO:K16823]
100442613  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
100174337  LLGL2; lethal(2) giant larvae protein homolog 2 [KO:K06094]
100441933  SCRIB; protein scribble homolog isoform X1 [KO:K16175]
100444925  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
100440838  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
100447431  DLG3; disks large homolog 3 isoform X1 [KO:K21098]
100453630  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
100449311  DLG5; disks large homolog 5 isoform X1 [KO:K24050]
100172245  CSNK1D; casein kinase I isoform delta [KO:K08959] [EC:2.7.11.1]
100447547  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
100171847  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
100432610  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
100433100  TP73; tumor protein p73 isoform X1 [KO:K10148]
100452429  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
100456357  TEAD3; transcriptional enhancer factor TEF-5 [KO:K09448]
100453732  TEAD4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
100432550  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
100461589  TEAD2; transcriptional enhancer factor TEF-4 isoform X3 [KO:K09448]
100437145  CTGF; connective tissue growth factor [KO:K06827]
100461064  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
100443606  AREG; amphiregulin [KO:K09782]
100172652  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
100435621  AFP; alpha-fetoprotein [KO:K16144]
100451938  ITGB2; integrin beta-2 [KO:K06464]
100174103  FGF1; fibroblast growth factor 1 [KO:K18496]
100459982  TGFB1; transforming growth factor beta-1 [KO:K13375]
100461291  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
100433208  TGFB3; transforming growth factor beta-3 [KO:K13377]
100450864  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
100459236  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
100460706  SMAD7; mothers against decapentaplegic homolog 7 [KO:K19631]
100173357  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
100448249  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100439171  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100435876  SERPINE1; LOW QUALITY PROTEIN: plasminogen activator inhibitor 1 [KO:K03982]
100460853  BMP2; bone morphogenetic protein 2 [KO:K21283]
100449444  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
100458055  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
100445825  BMP6; bone morphogenetic protein 6 [KO:K16620]
100434378  BMP7; bone morphogenetic protein 7 [KO:K16621]
100445772  BMP8B; bone morphogenetic protein 8B [KO:K16622]
103892933  bone morphogenetic protein 8B-like [KO:K16622]
100452554  GDF5; growth/differentiation factor 5 [KO:K04664]
100440841  GDF6; growth/differentiation factor 6 [KO:K20012]
100443944  GDF7; growth/differentiation factor 7 [KO:K20013]
100448030  AMH; muellerian-inhibiting factor [KO:K04665]
100450136  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100444576  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
100441517  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
100432108  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
100445861  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
100172180  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100441356  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100137034  WNT2; protein Wnt-2 precursor [KO:K00182]
100460815  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
100431449  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100448240  WNT3A; protein Wnt-3a isoform X1 [KO:K00312]
100436330  WNT4; protein Wnt-4 [KO:K00408]
100174132  WNT5B; protein Wnt-5b precursor [KO:K00444]
100447525  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100440643  WNT6; protein Wnt-6 [KO:K00445]
100451196  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
100441147  WNT7A; protein Wnt-7a [KO:K00572]
100450268  WNT8B; protein Wnt-8b [KO:K00714]
100448766  WNT8A; protein Wnt-8a isoform X1 [KO:K00714]
100462535  WNT9B; protein Wnt-9b isoform X1 [KO:K01064]
100452135  WNT9A; protein Wnt-9a [KO:K01064]
100440744  WNT10B; protein Wnt-10b [KO:K01357]
100441013  WNT10A; protein Wnt-10a [KO:K01357]
100443554  WNT11; protein Wnt-11 [KO:K01384]
100452466  WNT16; protein Wnt-16 [KO:K01558]
100437467  FZD7; frizzled-7 [KO:K02432]
100444369  FZD1; frizzled-1 [KO:K02432]
100452043  FZD2; frizzled-2 [KO:K02235]
100457942  FZD3; frizzled-3 [KO:K02329]
100447615  FZD4; frizzled-4 [KO:K02354]
100458618  FZD5; frizzled-5 [KO:K02375]
112135184  FZD8; frizzled-8 [KO:K02375]
100172142  FZD6; frizzled-6 precursor [KO:K02376]
100442825  FZD10; frizzled-10 [KO:K02842]
100438736  FZD9; frizzled-9 [KO:K02842]
100448038  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100454488  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100454011  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X2 [KO:K02353]
100173609  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
100137177  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
100171925  YWHAQ; 14-3-3 protein theta [KO:K16197]
100455220  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
112131710  14-3-3 protein epsilon-like isoform X1 [KO:K06630]
100434385  YWHAH; 14-3-3 protein eta [KO:K16198]
100174383  YWHAG; 14-3-3 protein gamma [KO:K16198]
100447772  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100173739  CTNNB1; catenin beta-1 [KO:K02105]
100431482  APC; adenomatous polyposis coli protein isoform X2 [KO:K02085]
100435472  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
100434225  AXIN1; axin-1 isoform X1 [KO:K02157]
100431721  AXIN2; axin-2 isoform X1 [KO:K04385]
100461343  NKD2; protein naked cuticle homolog 2 isoform X1 [KO:K03213]
100437598  NKD1; protein naked cuticle homolog 1 [KO:K03213]
100461234  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100436197  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100434811  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
100447785  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100456735  MYC; myc proto-oncogene protein [KO:K04377]
100171625  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100457978  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100452570  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100460719  SOX2; transcription factor SOX-2 [KO:K16796]
100432144  SNAI2; zinc finger protein SNAI2 [KO:K05706]
100457858  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100457249  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100441387  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100173832  ACTB; actin, cytoplasmic 1 [KO:K05692]
100174076  CTNNA2; catenin alpha-2 [KO:K05691]
100453792  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
pon04120  Ubiquitin mediated proteolysis
pon04310  Wnt signaling pathway
pon04350  TGF-beta signaling pathway
pon04520  Adherens junction
pon04530  Tight junction
KO pathway
ko04390   
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