KEGG   PATHWAY: lww04390
Entry
lww04390                    Pathway                                
Name
Hippo signaling pathway - Leptonychotes weddellii (Weddell seal)
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
lww04390  Hippo signaling pathway
lww04390

Other DBs
GO: 0035329
Organism
Leptonychotes weddellii (Weddell seal) [GN:lww]
Gene
102746871  CRB1; protein crumbs homolog 1 isoform X1 [KO:K16681]
102732956  protein crumbs homolog 2 [KO:K16681]
102733787  partitioning defective 3 homolog [KO:K04237]
102750707  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
102739260  PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
102747056  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
102750732  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
102733069  PATJ; inaD-like protein [KO:K06092]
102737275  MPP5; MAGUK p55 subfamily member 5 isoform X1 [KO:K06091]
102746561  AMOT; angiomotin [KO:K16819]
102746331  YAP1; transcriptional coactivator YAP1 [KO:K16687]
102744093  WW domain-containing transcription regulator protein 1-like [KO:K16820]
102736035  LOW QUALITY PROTEIN: cadherin-1-like [KO:K05689]
102728802  CDH1; cadherin-1 [KO:K05689]
102735453  LIM domain-containing protein ajuba [KO:K16682]
102728951  LIMD1; LIM domain-containing protein 1 [KO:K16682]
102728027  NF2; merlin [KO:K16684]
102742316  WWC1; protein KIBRA [KO:K16685]
102740656  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
102737859  SAV1; protein salvador homolog 1 isoform X1 [KO:K16686]
102732656  STK3; serine/threonine-protein kinase 3 isoform X1 [KO:K04412]
102736655  ras association domain-containing protein 6 [KO:K09854]
102750450  RASSF1; ras association domain-containing protein 1 [KO:K09850]
102741460  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102748566  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
102732031  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
102730629  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
102731291  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
102732583  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
102744631  LATS1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
102750865  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
102737750  MOB1B; MOB kinase activator 1B isoform X1 [KO:K06685]
102733573  MOB1A; MOB kinase activator 1A [KO:K06685]
102728037  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
102744224  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102739955  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102743142  apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
102734257  LLGL scribble cell polarity complex component 2 [KO:K06094]
115937902  LLGL1; lethal(2) giant larvae protein homolog 1 [KO:K06094]
102733607  SCRIB; protein scribble homolog isoform X1 [KO:K16175]
102742814  DLG1; disks large homolog 1 [KO:K12076]
102730853  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
102740488  DLG3; disks large homolog 3 isoform X4 [KO:K21098]
102737201  DLG4; disks large homolog 4 isoform X3 [KO:K11828]
102740599  DLG5; disks large homolog 5 [KO:K24050]
102737207  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
102745518  CSNK1E; casein kinase I isoform X3 [KO:K08960] [EC:2.7.11.1]
102733743  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
102731981  F-box/WD repeat-containing protein 11-like [KO:K03362]
102744583  TP73; tumor protein p73 [KO:K10148]
102750827  BBC3; bcl-2-binding component 3 [KO:K10132]
102731083  TEAD4; transcriptional enhancer factor TEF-3 [KO:K09448]
102736942  transcriptional enhancer factor TEF-4-like [KO:K09448]
102742917  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
102728230  TEAD3; transcriptional enhancer factor TEF-5 isoform X4 [KO:K09448]
102732432  transcriptional enhancer factor TEF-4-like isoform X1 [KO:K09448]
102748776  CCN2; CCN family member 2 [KO:K06827]
102741253  AREG; amphiregulin [KO:K09782]
102731151  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
102736849  AFP; alpha-fetoprotein isoform X1 [KO:K16144]
102725651  ITGB2; integrin beta-2 [KO:K06464]
102749895  fibroblast growth factor 1-like [KO:K18496]
102747528  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
102727105  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
102738835  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
102741398  TGF-beta receptor type-1-like [KO:K04674] [EC:2.7.11.30]
102740086  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102736786  mothers against decapentaplegic homolog 7 [KO:K19631]
102730764  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
102730318  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
102738394  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
102736969  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
102731853  BMP2; bone morphogenetic protein 2 [KO:K21283]
102740547  BMP4; bone morphogenetic protein 4 isoform X2 [KO:K04662]
102726742  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
102740714  BMP7; bone morphogenetic protein 7 [KO:K16621]
102725942  bone morphogenetic protein 8A [KO:K16622]
102748713  GDF5; growth/differentiation factor 5 [KO:K04664]
102733319  GDF7; growth/differentiation factor 7 [KO:K20013]
102737112  AMH; muellerian-inhibiting factor [KO:K04665]
102751051  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
102749651  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
102743492  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
102739027  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
102726544  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
102726330  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
102730706  WNT1; proto-oncogene Wnt-1 [KO:K03209]
102738348  WNT2; protein Wnt-2 [KO:K00182]
102738250  WNT2B; protein Wnt-2b [KO:K00182]
102731293  WNT3A; protein Wnt-3a [KO:K00312]
102726133  WNT3; proto-oncogene Wnt-3 [KO:K00312]
102747510  WNT4; protein Wnt-4 [KO:K00408]
102726812  WNT5A; protein Wnt-5a isoform X2 [KO:K00444]
102736290  WNT5B; protein Wnt-5b [KO:K00444]
102749681  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
102739552  protein Wnt-7b [KO:K00572]
102732238  protein Wnt-7a-like [KO:K00572]
102738659  WNT8B; protein Wnt-8b [KO:K00714]
102729143  WNT8A; protein Wnt-8a [KO:K00714]
102751255  WNT9B; protein Wnt-9b [KO:K01064]
102740881  WNT10B; protein Wnt-10b [KO:K01357]
102726929  WNT10A; protein Wnt-10a [KO:K01357]
102733699  WNT11; protein Wnt-11 [KO:K01384]
102726484  protein Wnt-16 [KO:K01558]
102739492  FZD7; frizzled-7 [KO:K02432]
102726140  FZD1; frizzled-1 [KO:K02432]
102729642  FZD2; frizzled-2 [KO:K02235]
102743290  FZD3; frizzled-3 [KO:K02329]
102743445  FZD4; frizzled-4 [KO:K02354]
102751215  FZD5; frizzled-5 [KO:K02375]
102727415  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
102731813  frizzled-6 [KO:K02376]
102744247  FZD9; frizzled-9 [KO:K02842]
102744652  FZD10; frizzled-10 [KO:K02842]
102726086  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
102730962  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X2 [KO:K02353]
102736689  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
102736059  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
102742022  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
102750756  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102736014  YWHAH; 14-3-3 protein eta [KO:K16198]
102729432  YWHAG; 14-3-3 protein gamma [KO:K16198]
102742516  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102750710  catenin beta-1 [KO:K02105]
102731320  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
102733516  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
102732857  AXIN1; axin-1 isoform X1 [KO:K02157]
102731641  AXIN2; axin-2 isoform X1 [KO:K04385]
102732143  NKD1; protein naked cuticle homolog 1 [KO:K03213]
102725842  NKD2; protein naked cuticle homolog 2 [KO:K03213]
102733939  TCF7; transcription factor 7 isoform X1 [KO:K02620]
102731685  TCF7L1; transcription factor 7-like 1 isoform X2 [KO:K04490]
102745990  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
102737827  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
102739954  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
102747216  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102747548  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102736121  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
102729919  SOX2; transcription factor SOX-2 [KO:K16796]
102744569  SNAI2; zinc finger protein SNAI2 [KO:K05706]
102746032  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
102740856  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
102736013  ACTG1; actin, cytoplasmic 2 [KO:K05692]
102744309  ACTB; actin, cytoplasmic 1 [KO:K05692]
102730092  catenin alpha-3 [KO:K05691]
102738933  catenin alpha-3 [KO:K05691]
102735878  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
lww04120  Ubiquitin mediated proteolysis
lww04310  Wnt signaling pathway
lww04350  TGF-beta signaling pathway
lww04520  Adherens junction
lww04530  Tight junction
KO pathway
ko04390   
LinkDB

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