KEGG   PATHWAY: gas04390
Entry
gas04390                    Pathway                                
Name
Hippo signaling pathway - Gracilinanus agilis (agile gracile opossum)
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
gas04390  Hippo signaling pathway
gas04390

Other DBs
GO: 0035329
Organism
Gracilinanus agilis (agile gracile opossum) [GN:gas]
Gene
123233695  CRB2; protein crumbs homolog 2 [KO:K16681]
123245943  CRB1; protein crumbs homolog 1 [KO:K16681]
123248808  PARD3; partitioning defective 3 homolog isoform X1 [KO:K04237]
123254010  partitioning defective 6 homolog alpha-like isoform X1 [KO:K06093]
123239980  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
123234641  PARD6A; partitioning defective 6 homolog alpha [KO:K06093]
123235060  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
123240168  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
123242057  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
123245770  PATJ; inaD-like protein [KO:K06092]
123253452  uncharacterized protein LOC123253452 [KO:K06091]
123233987  PALS1; protein PALS1 [KO:K06091]
123240788  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
123241974  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
123246829  LOW QUALITY PROTEIN: WW domain-containing transcription regulator protein 1-like [KO:K16820]
123236751  CDH1; cadherin-1 isoform X1 [KO:K05689]
123235346  Wilms tumor protein 1-interacting protein [KO:K16682]
123237994  AJUBA; LIM domain-containing protein ajuba [KO:K16682]
123245346  NF2; merlin isoform X1 [KO:K16684]
123246827  merlin-like [KO:K16684]
123237501  WWC1; protein KIBRA [KO:K16685]
123246674  FRMD1; FERM domain-containing protein 1 [KO:K16821]
123237672  FRMD6; FERM domain-containing protein 6 [KO:K16822]
123237676  SAV1; protein salvador homolog 1 [KO:K16686]
123240899  STK3; serine/threonine-protein kinase 3 [KO:K04412]
123250940  RASSF6; ras association domain-containing protein 6 [KO:K09854]
123247685  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
123237637  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123251011  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123252361  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
123241835  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
123240795  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
123235614  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
123236652  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
123233025  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
123251504  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
123245726  LATS1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
123240611  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
123236647  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
123252023  MOB1B; MOB kinase activator 1B [KO:K06685]
123237064  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
123244865  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123252171  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
123252806  serine/threonine-protein phosphatase PP1-alpha catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
123246004  TP53BP2; LOW QUALITY PROTEIN: apoptosis-stimulating of p53 protein 2 [KO:K16823]
123235579  LLGL1; lethal(2) giant larvae protein homolog 1 [KO:K06094]
123244403  LLGL2; LLGL scribble cell polarity complex component 2 [KO:K06094]
123242156  SCRIB; protein scribble homolog [KO:K16175]
123242790  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
123241232  DLG2; disks large homolog 2 [KO:K12075]
123244463  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
123234332  DLG5; disks large homolog 5 [KO:K24050]
123247434  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
123250350  CSNK1E; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
123237495  FBXW11; F-box/WD repeat-containing protein 11 [KO:K03362]
123238130  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
123256076  BBC3; bcl-2-binding component 3 isoform X1 [KO:K10132]
123250053  TEAD4; transcriptional enhancer factor TEF-3 [KO:K09448]
123245399  TEAD3; transcriptional enhancer factor TEF-5 [KO:K09448]
123252069  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
123245578  CCN2; CCN family member 2 [KO:K06827]
123242298  GLI2; zinc finger protein GLI2 [KO:K16798]
123251051  AREG; amphiregulin [KO:K09782]
123231659  baculoviral IAP repeat-containing protein 5-like [KO:K08731]
123245520  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
123251873  alpha-fetoprotein [KO:K16144]
123247645  ITGB2; integrin beta-2 [KO:K06464]
123235626  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
123256028  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
123247856  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
123235863  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123231024  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
123249688  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
123237705  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
123237729  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
123238038  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
123253784  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4-like [KO:K04501]
123254358  mothers against decapentaplegic homolog 4-like [KO:K04501]
123237642  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
123245045  SERPINE1; plasminogen activator inhibitor 1 isoform X1 [KO:K03982]
123234308  bone morphogenetic protein 2-like [KO:K21283]
123234746  BMP2; bone morphogenetic protein 2 [KO:K21283]
123235751  BMP4; bone morphogenetic protein 4 [KO:K04662]
123247109  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
123240342  BMP6; bone morphogenetic protein 6 [KO:K16620]
123233560  BMP7; bone morphogenetic protein 7 [KO:K16621]
123243249  BMP8A; bone morphogenetic protein 8A [KO:K16622]
123256692  GDF5; growth/differentiation factor 5 [KO:K04664]
123231898  GDF6; growth/differentiation factor 6 [KO:K20012]
123243849  AMH; muellerian-inhibiting factor [KO:K04665]
123234379  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
123253139  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
123242702  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
123252994  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
123235417  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
123234940  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
123250610  WNT1; LOW QUALITY PROTEIN: proto-oncogene Wnt-1 [KO:K03209]
123247175  WNT2B; protein Wnt-2b [KO:K00182]
123249353  WNT2; protein Wnt-2 [KO:K00182]
123247288  WNT3; proto-oncogene Wnt-3 [KO:K00312]
123247916  WNT3A; protein Wnt-3a [KO:K00312]
123241007  WNT4; protein Wnt-4 [KO:K00408]
123248652  WNT5B; protein Wnt-5b [KO:K00444]
123246628  WNT5A; protein Wnt-5a [KO:K00444]
123241934  WNT6; protein Wnt-6 [KO:K00445]
123230733  WNT7A; protein Wnt-7a [KO:K00572]
123249395  WNT7B; protein Wnt-7b [KO:K00572]
123235661  WNT8A; protein Wnt-8a [KO:K00714]
123236479  WNT8B; protein Wnt-8b [KO:K00714]
123247924  WNT9A; protein Wnt-9a [KO:K01064]
123245481  WNT9B; LOW QUALITY PROTEIN: protein Wnt-9b [KO:K01064]
123250246  WNT10B; protein Wnt-10b [KO:K01357]
123240153  WNT10A; protein Wnt-10a [KO:K01357]
123241223  WNT11; protein Wnt-11 [KO:K01384]
123249618  WNT16; protein Wnt-16 [KO:K01558]
123249797  FZD1; frizzled-1 [KO:K02432]
123240083  FZD7; frizzled-7 [KO:K02432]
123245351  FZD2; frizzled-2 [KO:K02235]
123233406  FZD3; frizzled-3 [KO:K02329]
123233407  frizzled-3 [KO:K02329]
123238807  FZD4; frizzled-4 [KO:K02354]
123248970  FZD8; frizzled-8 [KO:K02375]
123240104  FZD5; frizzled-5 [KO:K02375]
123231917  FZD6; frizzled-6 [KO:K02376]
123247520  FZD9; frizzled-9 [KO:K02842]
123255006  FZD10; frizzled-10 [KO:K02842]
123244461  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
123244708  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
123240119  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
123235790  YWHAQ; 14-3-3 protein theta [KO:K16197]
123237744  14-3-3 protein zeta/delta-like [KO:K16197]
123245069  14-3-3 protein zeta/delta-like [KO:K16197]
123234719  14-3-3 protein zeta/delta-like [KO:K16197]
123235041  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
123240956  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
123253939  14-3-3 protein epsilon-like [KO:K06630]
123236441  14-3-3 protein epsilon [KO:K06630]
123244438  YWHAE; 14-3-3 protein epsilon [KO:K06630]
123247526  YWHAG; 14-3-3 protein gamma [KO:K16198]
123230419  YWHAH; 14-3-3 protein eta [KO:K16198]
123242376  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123250437  CTNNB1; catenin beta-1 [KO:K02105]
123235937  APC; adenomatous polyposis coli protein [KO:K02085]
123256777  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
123231357  AXIN1; axin-1 isoform X1 [KO:K02157]
123247857  AXIN2; axin-2 [KO:K04385]
123235303  NKD1; protein naked cuticle homolog 1 [KO:K03213]
123238000  NKD2; protein naked cuticle homolog 2 [KO:K03213]
123237636  TCF7; transcription factor 7 [KO:K02620]
123233138  TCF7L1; transcription factor 7-like 1 [KO:K04490]
123238173  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
123241543  MYC; myc proto-oncogene protein [KO:K04377]
123250729  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
123245608  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
123253804  sex-determining region Y protein-like [KO:K16796]
123240329  SOX2; transcription factor SOX-2 [KO:K16796]
123255397  SNAI2; zinc finger protein SNAI2 [KO:K05706]
123238988  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
123240870  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
123232980  actin, cytoplasmic type 5 [KO:K05692]
123247581  actin, cytoplasmic 1-like isoform X1 [KO:K05692]
123242607  actin, cytoplasmic 2-like isoform X1 [KO:K05692]
123243855  actin, cytoplasmic 2-like isoform X1 [KO:K05692]
123243954  actin, cytoplasmic 2 isoform X1 [KO:K05692]
123244269  actin, cytoplasmic 1-like isoform X1 [KO:K05692]
123244479  ACTG1; actin, cytoplasmic 2 [KO:K05692]
123251262  LOW QUALITY PROTEIN: actin-like [KO:K05692]
123233915  ACTB; actin, cytoplasmic 1 [KO:K05692]
123252825  actin-3-like [KO:K05692]
123234757  actin, cytoplasmic 1-like isoform X1 [KO:K05692]
123234907  actin, cytoplasmic 1-like [KO:K05692]
123237572  CTNNA1; catenin alpha-1 [KO:K05691]
123233098  CTNNA2; catenin alpha-2 [KO:K05691]
123234417  CTNNA3; catenin alpha-3 [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
gas04120  Ubiquitin mediated proteolysis
gas04310  Wnt signaling pathway
gas04350  TGF-beta signaling pathway
gas04520  Adherens junction
gas04530  Tight junction
KO pathway
ko04390   
LinkDB

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