KEGG   PATHWAY: pps04390
Entry
pps04390                    Pathway                                
Name
Hippo signaling pathway - Pan paniscus (bonobo)
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
pps04390  Hippo signaling pathway
pps04390

Other DBs
GO: 0035329
Organism
Pan paniscus (bonobo) [GN:pps]
Gene
100994311  CRB1; protein crumbs homolog 1 isoform X2 [KO:K16681]
100972299  CRB2; protein crumbs homolog 2 isoform X2 [KO:K16681]
100990710  PARD3; partitioning defective 3 homolog isoform X1 [KO:K04237]
100982056  PARD6A; partitioning defective 6 homolog alpha isoform X2 [KO:K06093]
100976443  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
100969313  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
100987713  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
100979245  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
100984381  PATJ; inaD-like protein isoform X1 [KO:K06092]
100970838  PALS1; protein PALS1 isoform X2 [KO:K06091]
100993839  AMOT; angiomotin isoform X1 [KO:K16819]
100988662  YAP1; transcriptional coactivator YAP1 isoform X1 [KO:K16687]
100987843  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
100989112  CDH1; cadherin-1 [KO:K05689]
100985823  AJUBA; LIM domain-containing protein ajuba isoform X1 [KO:K16682]
100978590  LIMD1; LIM domain-containing protein 1 isoform X1 [KO:K16682]
100994915  NF2; merlin isoform X1 [KO:K16684]
100970516  WWC1; protein KIBRA isoform X7 [KO:K16685]
100993372  FRMD1; FERM domain-containing protein 1 isoform X2 [KO:K16821]
100971681  FRMD6; FERM domain-containing protein 6 isoform X2 [KO:K16822]
100977676  SAV1; protein salvador homolog 1 isoform X1 [KO:K16686]
117974336  protein salvador homolog 1 isoform X2 [KO:K16686]
100992217  STK3; serine/threonine-protein kinase 3 isoform X2 [KO:K04412]
100978903  RASSF6; ras association domain-containing protein 6 isoform X1 [KO:K09854]
100975339  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
100987323  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100981626  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
100976101  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100995920  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100991308  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X6 [KO:K03456]
100983884  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X2 [KO:K04354]
100991998  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
100990236  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X6 [KO:K04354]
100968814  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
100990270  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
100991443  serine/threonine-protein kinase LATS1 isoform X3 [KO:K08791] [EC:2.7.11.1]
103784525  MOB1B; MOB kinase activator 1B isoform X2 [KO:K06685]
100994893  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
100992486  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100974889  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100978326  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
134730135  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
134730136  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
100989224  TP53BP2; apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
100991928  LLGL2; LLGL scribble cell polarity complex component 2 isoform X3 [KO:K06094]
100973006  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X5 [KO:K06094]
100970225  SCRIB; protein scribble homolog isoform X1 [KO:K16175]
100987596  DLG1; disks large homolog 1 isoform X33 [KO:K12076]
100982329  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
100987358  DLG3; disks large homolog 3 isoform X1 [KO:K21098]
100985837  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
100996192  DLG5; disks large homolog 5 isoform X1 [KO:K24050]
100976391  CSNK1D; casein kinase I isoform X5 [KO:K08959] [EC:2.7.11.1]
100975570  CSNK1E; casein kinase I isoform X3 [KO:K08960] [EC:2.7.11.1]
100976100  FBXW11; F-box/WD repeat-containing protein 11 isoform X7 [KO:K03362]
100977066  BTRC; F-box/WD repeat-containing protein 1A isoform X10 [KO:K03362]
100968381  TP73; tumor protein p73 isoform X2 [KO:K10148]
100974112  BBC3; bcl-2-binding component 3 isoform X3 [KO:K10132]
100995540  TEAD4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
100974267  TEAD3; transcriptional enhancer factor TEF-5 isoform X1 [KO:K09448]
100969496  TEAD2; transcriptional enhancer factor TEF-4 isoform X1 [KO:K09448]
100995181  TEAD1; transcriptional enhancer factor TEF-1 isoform X1 [KO:K09448]
100989664  CCN2; CCN family member 2 [KO:K06827]
100973775  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
100980532  BIRC5; baculoviral IAP repeat-containing protein 5 isoform X1 [KO:K08731]
100980292  AFP; alpha-fetoprotein [KO:K16144]
100985940  ITGB2; integrin beta-2 [KO:K06464]
100972676  FGF1; LOW QUALITY PROTEIN: fibroblast growth factor 1 [KO:K18496]
100980947  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
100985755  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
100990987  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
100984463  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100985497  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
100982938  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
100980706  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100993322  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100991127  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100973457  SERPINE1; plasminogen activator inhibitor 1 isoform X2 [KO:K03982]
100967346  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
100987443  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
100989910  BMP5; bone morphogenetic protein 5 [KO:K04663]
100978224  BMP6; bone morphogenetic protein 6 [KO:K16620]
100979629  BMP7; bone morphogenetic protein 7 [KO:K16621]
100984543  bone morphogenetic protein 8A [KO:K16622]
117980585  BMP8B; bone morphogenetic protein 8B isoform X1 [KO:K16622]
100984668  GDF5; growth/differentiation factor 5 [KO:K04664]
100974799  GDF6; growth/differentiation factor 6 [KO:K20012]
100970378  GDF7; growth/differentiation factor 7 [KO:K20013]
100970224  AMH; muellerian-inhibiting factor [KO:K04665]
100973488  BMPR1A; bone morphogenetic protein receptor type-1A isoform X1 [KO:K04673] [EC:2.7.11.30]
100967284  bone morphogenetic protein receptor type-1A-like [KO:K04673] [EC:2.7.11.30]
100991587  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
100987362  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
100992068  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
100994269  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
100985375  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100995465  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100990322  WNT2; protein Wnt-2 [KO:K00182]
100983371  WNT2B; protein Wnt-2b [KO:K00182]
100992553  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100977143  WNT3A; protein Wnt-3a [KO:K00312]
100992168  WNT4; protein Wnt-4 [KO:K00408]
100990957  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100975676  WNT5B; protein Wnt-5b isoform X2 [KO:K00444]
100987794  WNT6; protein Wnt-6 [KO:K00445]
100995012  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
100977315  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
100993563  WNT8A; protein Wnt-8a isoform X1 [KO:K00714]
130540558  WNT8B; protein Wnt-8b [KO:K00714]
100993261  WNT9B; protein Wnt-9b isoform X1 [KO:K01064]
100986204  WNT9A; protein Wnt-9a [KO:K01064]
100995123  WNT10B; protein Wnt-10b [KO:K01357]
100988140  WNT10A; protein Wnt-10a [KO:K01357]
100989115  WNT11; protein Wnt-11 [KO:K01384]
100985948  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
100983788  FZD7; frizzled-7 [KO:K02432]
103784670  FZD1; frizzled-1 [KO:K02432]
100994538  FZD2; frizzled-2 [KO:K02235]
100984879  FZD3; frizzled-3 isoform X1 [KO:K02329]
100984214  FZD4; frizzled-4 [KO:K02354]
100977034  FZD5; frizzled-5 [KO:K02375]
117974549  FZD8; frizzled-8 [KO:K02375]
100980889  FZD6; frizzled-6 [KO:K02376]
100977692  FZD10; frizzled-10 [KO:K02842]
100982738  FZD9; frizzled-9 [KO:K02842]
100977837  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100986952  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100991559  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100983141  YWHAB; 14-3-3 protein beta/alpha isoform X4 [KO:K16197]
100977477  YWHAZ; 14-3-3 protein zeta/delta isoform X2 [KO:K16197]
103786771  14-3-3 protein theta-like [KO:K16197]
100991126  YWHAQ; 14-3-3 protein theta [KO:K16197]
100967426  14-3-3 protein zeta/delta-like [KO:K16197]
117977099  14-3-3 protein zeta/delta [KO:K16197]
100975327  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100978515  14-3-3 protein epsilon-like [KO:K06630]
100992216  YWHAH; 14-3-3 protein eta [KO:K16198]
100994439  YWHAG; 14-3-3 protein gamma [KO:K16198]
100972306  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100982035  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
100992823  APC; adenomatous polyposis coli protein isoform X9 [KO:K02085]
129394699  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
100986279  AXIN1; axin-1 isoform X1 [KO:K02157]
100990800  AXIN2; axin-2 isoform X1 [KO:K04385]
100978387  NKD1; protein naked cuticle homolog 1 [KO:K03213]
134730411  NKD2; protein naked cuticle homolog 2 isoform X1 [KO:K03213]
100980839  TCF7; transcription factor 7 isoform X2 [KO:K02620]
100968002  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
100978424  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
100995847  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
103786410  MYC; myc proto-oncogene protein [KO:K04377]
100995605  CCND1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
100990850  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100972595  CCND3; G1/S-specific cyclin-D3 isoform X2 [KO:K10152]
100974432  SOX2; transcription factor SOX-2 [KO:K16796]
100979404  SNAI2; zinc finger protein SNAI2 [KO:K05706]
100970636  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X2 [KO:K16060]
100971429  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100970542  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100987964  LOW QUALITY PROTEIN: actin-like [KO:K05692]
100990579  actin, cytoplasmic 1 [KO:K05692]
129398212  ACTB; actin, cytoplasmic 1 [KO:K05692]
100988691  CTNNA2; catenin alpha-2 isoform X2 [KO:K05691]
100983736  CTNNA1; catenin alpha-1 isoform X1 [KO:K05691]
100985984  CTNNA3; catenin alpha-3 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
pps04120  Ubiquitin mediated proteolysis
pps04310  Wnt signaling pathway
pps04350  TGF-beta signaling pathway
pps04520  Adherens junction
pps04530  Tight junction
KO pathway
ko04390   
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