KEGG   PATHWAY: mcc04390
Entry
mcc04390                    Pathway                                
Name
Hippo signaling pathway - Macaca mulatta (rhesus monkey)
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
mcc04390  Hippo signaling pathway
mcc04390

Other DBs
GO: 0035329
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100423838  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100424087  AXIN1; axin-1 isoform X1 [KO:K02157]
100427030  BMP8B; bone morphogenetic protein 8B [KO:K16622]
100429858  TEAD3; transcriptional enhancer factor TEF-5 isoform X1 [KO:K09448]
106992315  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
114669766  [KO:K09448]
114675335  [KO:K04388] [EC:2.7.11.30]
574265  CTNNB1; catenin beta-1 [KO:K02105]
574285  ACTB; actin, cytoplasmic 1 [KO:K05692]
574320  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
574340  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
574352  PRKCI; protein kinase C iota type isoform X1 [KO:K06069] [EC:2.7.11.13]
574385  CTNNA1; catenin alpha-1 [KO:K05691]
693394  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
693419  WNT7A; protein Wnt-7a [KO:K00572]
693443  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
694069  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
694078  FRMD1; FERM domain-containing protein 1 isoform X1 [KO:K16821]
694560  TCF7L1; transcription factor 7-like 1 isoform X2 [KO:K04490]
694618  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
694625  FZD6; frizzled-6 precursor [KO:K02376]
694626  MYC; myc proto-oncogene protein [KO:K04377]
694702  YWHAQ; 14-3-3 protein theta [KO:K16197]
695065  CRB2; protein crumbs homolog 2 isoform X1 [KO:K16681]
695091  BMP6; bone morphogenetic protein 6 [KO:K16620]
695118  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
695164  TP73; tumor protein p73 isoform X1 [KO:K10148]
695215  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
695776  LEF1; lymphoid enhancer-binding factor 1 isoform X3 [KO:K04492]
696040  CTNNA3; catenin alpha-3 [KO:K05691]
696131  LATS1; serine/threonine-protein kinase LATS1 isoform X1 [KO:K08791] [EC:2.7.11.1]
696200  WNT3A; protein Wnt-3a [KO:K00312]
696326  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
696845  WNT11; protein Wnt-11 isoform X2 [KO:K01384]
696898  BMPR1A; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:2.7.11.30]
696948  BMP7; bone morphogenetic protein 7 [KO:K16621]
697179  DLG3; disks large homolog 3 [KO:K21098]
697581  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
698036  NKD1; protein naked cuticle homolog 1 [KO:K03213]
698338  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
698875  WWC1; protein KIBRA isoform X1 [KO:K16685]
699351  PARD6A; partitioning defective 6 homolog alpha [KO:K06093]
699479  PARD6G; partitioning defective 6 homolog gamma [KO:K06093]
699520  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
699957  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
700565  CSNK1E; casein kinase I isoform epsilon [KO:K08960] [EC:2.7.11.1]
700573  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
700692  WNT10A; protein Wnt-10a [KO:K01357]
700954  TEAD1; transcriptional enhancer factor TEF-1 isoform X9 [KO:K09448]
701126  GDF6; growth/differentiation factor 6 [KO:K20012]
701759  TCF7L2; transcription factor 7-like 2 isoform X9 [KO:K04491]
701803  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
702385  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
702396  AREG; amphiregulin [KO:K09782]
702462  GDF7; growth/differentiation factor 7 [KO:K20013]
702468  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
702592  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
703064  FZD7; frizzled-7 [KO:K02432]
703088  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
703123  DLG5; disks large homolog 5 isoform X2 [KO:K24050]
703239  TGFB3; transforming growth factor beta-3 precursor [KO:K13377]
703302  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
703942  FZD1; frizzled-1 [KO:K02432]
704010  [KO:K16197]
704088  BMPR2; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:2.7.11.30]
704382  YAP1; transcriptional coactivator YAP1 isoform X4 [KO:K16687]
704387  CDH1; cadherin-1 [KO:K05689]
704459  RASSF6; ras association domain-containing protein 6 [KO:K09854]
704754  FZD4; frizzled-4 precursor [KO:K02354]
704786  AFP; alpha-fetoprotein [KO:K16144]
704826  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
704991  WNT2; protein Wnt-2 precursor [KO:K00182]
705155  MOB1B; MOB kinase activator 1B isoform X1 [KO:K06685]
705383  TP53BP2; apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
705432  GDF5; growth/differentiation factor 5 [KO:K04664]
705474  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
705671  [KO:K05692]
705692  WNT5A; protein Wnt-5a isoform X2 [KO:K00444]
705773  WNT2B; protein Wnt-2b [KO:K00182]
705864  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
705877  GLI2; zinc finger protein GLI2 [KO:K16798]
705970  FGF1; fibroblast growth factor 1 [KO:K18496]
706424  SAV1; protein salvador homolog 1 [KO:K16686]
706472  PARD3; partitioning defective 3 homolog isoform X1 [KO:K04237]
706973  LLGL2; lethal(2) giant larvae protein homolog 2 isoform X1 [KO:K06094]
706988  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
707039  SOX2; transcription factor SOX-2 [KO:K16796]
707266  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
707345  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
707405  LLGL1; lethal(2) giant larvae protein homolog 1 isoform X1 [KO:K06094]
707425  STK3; serine/threonine-protein kinase 3 [KO:K04412]
707540  TGFB2; transforming growth factor beta-2 precursor [KO:K13376]
707701  AMOT; angiomotin isoform X1 [KO:K16819]
707864  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
707984  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
708368  FZD8; frizzled-8 [KO:K02375]
708906  WNT10B; protein Wnt-10b precursor [KO:K01357]
708962  SNAI2; zinc finger protein SNAI2 [KO:K05706]
708990  FBXW11; F-box/WD repeat-containing protein 11 [KO:K03362]
709009  WNT1; proto-oncogene Wnt-1 [KO:K03209]
709500  NKD2; protein naked cuticle homolog 2 [KO:K03213]
709565  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
709572  DLG1; disks large homolog 1 [KO:K12076]
709723  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
709935  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
710049  MPP5; MAGUK p55 subfamily member 5 isoform X1 [KO:K06091]
710234  TCF7; transcription factor 7 isoform X3 [KO:K02620]
710242  WNT8B; protein Wnt-8b [KO:K00714]
710326  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
710340  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
710379  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
710387  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
710577  ITGB2; integrin beta-2 isoform X1 [KO:K06464]
710796  FZD5; frizzled-5 [KO:K02375]
710991  CRB1; protein crumbs homolog 1 isoform X3 [KO:K16681]
711023  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
711355  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
711374  [KO:K16197]
711567  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
711843  BTRC; F-box/WD repeat-containing protein 1A isoform X2 [KO:K03362]
711920  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
711989  BMP5; bone morphogenetic protein 5 [KO:K04663]
712004  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
712135  CTNNA2; catenin alpha-2 [KO:K05691]
712381  FZD2; frizzled-2 [KO:K02235]
712865  AJUBA; LIM domain-containing protein ajuba [KO:K16682]
713114  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
713160  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
713687  ACTG1; actin, cytoplasmic 2 [KO:K05692]
713764  WNT8A; protein Wnt-8a [KO:K00714]
713839  FZD3; frizzled-3 precursor [KO:K02329]
713864  WNT7B; protein Wnt-7b isoform X2 [KO:K00572]
713883  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
714169  LIMD1; LIM domain-containing protein 1 isoform X1 [KO:K16682]
714273  DLG4; disks large homolog 4 [KO:K11828]
714381  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
714520  CCN2; connective tissue growth factor isoform X2 [KO:K06827]
714945  NF2; merlin [KO:K16684]
714952  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
715517  YWHAG; 14-3-3 protein gamma [KO:K16198]
716392  FZD9; frizzled-9 [KO:K02842]
716877  WNT9B; protein Wnt-9b [KO:K01064]
716909  WNT3; proto-oncogene Wnt-3 [KO:K00312]
717016  YWHAH; 14-3-3 protein eta [KO:K16198]
717539  AMH; muellerian-inhibiting factor [KO:K04665]
717788  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
717812  FZD10; frizzled-10 [KO:K02842]
717955  BBC3; bcl-2-binding component 3 [KO:K10132]
717999  WTIP; Wilms tumor protein 1-interacting protein isoform X1 [KO:K16682]
718330  BMP2; bone morphogenetic protein 2 [KO:K21283]
718566  AXIN2; axin-2 isoform X1 [KO:K04385]
718677  [KO:K16622]
718703  TEAD2; transcriptional enhancer factor TEF-4 isoform X3 [KO:K09448]
719263  PATJ; inaD-like protein isoform X1 [KO:K06092]
719479  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
719929  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
720156  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
721685  WNT5B; protein Wnt-5b [KO:K00444]
721735  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
721772  TEAD4; transcriptional enhancer factor TEF-3 isoform X1 [KO:K09448]
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
mcc04120  Ubiquitin mediated proteolysis
mcc04310  Wnt signaling pathway
mcc04350  TGF-beta signaling pathway
mcc04520  Adherens junction
mcc04530  Tight junction
KO pathway
ko04390   

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