KEGG   PATHWAY: pcoo04390
Entry
pcoo04390                   Pathway                                
Name
Hippo signaling pathway - Puma concolor (puma)
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
pcoo04390  Hippo signaling pathway
pcoo04390

Other DBs
GO: 0035329
Organism
Puma concolor (puma) [GN:pcoo]
Gene
112850412  CRB2; protein crumbs homolog 2 [KO:K16681]
112857693  CRB1; protein crumbs homolog 1 [KO:K16681]
112867938  PARD3; partitioning defective 3 homolog [KO:K04237]
112869298  PARD6B; partitioning defective 6 homolog beta [KO:K06093]
112857433  PARD6A; partitioning defective 6 homolog alpha isoform X1 [KO:K06093]
112861986  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
112849338  PRKCI; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
112868723  PATJ; inaD-like protein [KO:K06092]
112855952  MPP5; MAGUK p55 subfamily member 5 [KO:K06091]
112870982  AMOT; angiomotin [KO:K16819]
112865901  YAP1; transcriptional coactivator YAP1 [KO:K16687]
112849488  WWTR1; WW domain-containing transcription regulator protein 1 [KO:K16820]
112857227  CDH1; cadherin-1 isoform X1 [KO:K05689]
112856102  AJUBA; LIM domain-containing protein ajuba isoform X1 [KO:K16682]
112870346  NF2; merlin isoform X1 [KO:K16684]
112860514  WWC1; protein KIBRA [KO:K16685]
112856012  FRMD6; FERM domain-containing protein 6 isoform X1 [KO:K16822]
112855762  SAV1; protein salvador homolog 1 [KO:K16686]
112859299  STK3; serine/threonine-protein kinase 3 [KO:K04412]
112858485  RASSF6; ras association domain-containing protein 6 [KO:K09854]
112852552  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
112870013  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
112860397  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
112850861  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
112866111  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
112869818  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
112859077  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
112860914  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
112862275  LATS1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
112861116  LATS2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
112868991  MOB1A; MOB kinase activator 1A isoform X1 [KO:K06685]
112858064  MOB1B; MOB kinase activator 1B isoform X1 [KO:K06685]
112870325  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
112864257  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
112851965  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
112863176  TP53BP2; apoptosis-stimulating of p53 protein 2 [KO:K16823]
112864507  LLGL2; lethal(2) giant larvae protein homolog 2 [KO:K06094]
112859681  SCRIB; protein scribble homolog [KO:K16175]
112849898  DLG1; disks large homolog 1 [KO:K12076]
112865005  DLG2; disks large homolog 2 isoform X1 [KO:K12075]
112871148  DLG3; disks large homolog 3 isoform X1 [KO:K21098]
112856981  DLG4; disks large homolog 4 [KO:K11828]
112854566  DLG5; disks large homolog 5 [KO:K24050]
112864604  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
112863936  CSNK1E; casein kinase I [KO:K08960] [EC:2.7.11.1]
112861536  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
112854311  BTRC; F-box/WD repeat-containing protein 1A [KO:K03362]
112848593  TP73; tumor protein p73 [KO:K10148]
112862840  TEAD3; transcriptional enhancer factor TEF-5 [KO:K09448]
112850996  TEAD2; transcriptional enhancer factor TEF-4 isoform X1 [KO:K09448]
112865305  TEAD1; transcriptional enhancer factor TEF-1 [KO:K09448]
112867920  TEAD4; transcriptional enhancer factor TEF-3 [KO:K09448]
112862635  CTGF; connective tissue growth factor [KO:K06827]
112865618  GLI2; LOW QUALITY PROTEIN: zinc finger protein GLI2 [KO:K16798]
112859021  AREG; amphiregulin [KO:K09782]
112864535  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
112858607  AFP; alpha-fetoprotein [KO:K16144]
112858735  alpha-fetoprotein-like [KO:K16144]
112849420  ITGB2; integrin beta-2 [KO:K06464]
112861306  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
112850697  TGFB1; transforming growth factor beta-1 [KO:K13375]
112864785  TGFB2; transforming growth factor beta-2 [KO:K13376]
112855350  TGFB3; transforming growth factor beta-3 [KO:K13377]
112851426  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
112850049  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
112868402  SMAD7; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 7 [KO:K19631]
112868176  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
112855310  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
112868129  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
112860099  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
112869247  BMP2; bone morphogenetic protein 2 [KO:K21283]
112855771  BMP4; bone morphogenetic protein 4 [KO:K04662]
112862219  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
112853410  BMP6; bone morphogenetic protein 6 [KO:K16620]
112869088  BMP7; bone morphogenetic protein 7 [KO:K16621]
112871789  BMP8A; bone morphogenetic protein 8A [KO:K16622]
112869272  GDF5; growth/differentiation factor 5 [KO:K04664]
112859751  GDF6; LOW QUALITY PROTEIN: growth/differentiation factor 6 [KO:K20012]
112864080  GDF7; growth/differentiation factor 7 [KO:K20013]
112854882  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
112858091  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
112871614  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
112858137  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
112869366  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
112864287  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
112867717  WNT1; proto-oncogene Wnt-1 [KO:K03209]
112848934  WNT2B; protein Wnt-2b [KO:K00182]
112866707  WNT2; protein Wnt-2 [KO:K00182]
112856886  WNT3A; protein Wnt-3a [KO:K00312]
112862190  WNT4; protein Wnt-4 [KO:K00408]
112852688  WNT5A; protein Wnt-5a [KO:K00444]
112867516  WNT5B; protein Wnt-5b [KO:K00444]
112867051  WNT6; protein Wnt-6 [KO:K00445]
112863403  WNT7B; protein Wnt-7b [KO:K00572]
112858017  WNT7A; protein Wnt-7a [KO:K00572]
112854316  WNT8B; protein Wnt-8b [KO:K00714]
112861375  WNT8A; protein Wnt-8a [KO:K00714]
112862200  WNT9B; protein Wnt-9b [KO:K01064]
112867060  WNT10A; protein Wnt-10a [KO:K01357]
112867618  WNT10B; protein Wnt-10b [KO:K01357]
112865757  WNT11; protein Wnt-11 [KO:K01384]
112867003  WNT16; protein Wnt-16 [KO:K01558]
112872031  FZD7; frizzled-7 [KO:K02432]
112866748  FZD1; frizzled-1 [KO:K02432]
112858405  FZD3; frizzled-3 [KO:K02329]
112865496  FZD4; frizzled-4 [KO:K02354]
112872259  FZD5; frizzled-5 [KO:K02375]
112867630  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
112859506  FZD6; frizzled-6 [KO:K02376]
112859899  FZD9; frizzled-9 [KO:K02842]
112849927  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
112870883  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
112869154  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
112864386  YWHAQ; 14-3-3 protein theta [KO:K16197]
112859599  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
112852258  YWHAE; LOW QUALITY PROTEIN: 14-3-3 protein epsilon [KO:K06630]
112870311  YWHAH; 14-3-3 protein eta [KO:K16198]
112859893  YWHAG; 14-3-3 protein gamma [KO:K16198]
112850475  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
112850292  CTNNB1; catenin beta-1 [KO:K02105]
112860216  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
112860062  AXIN1; axin-1 isoform X1 [KO:K02157]
112864471  AXIN2; axin-2 [KO:K04385]
112861711  NKD2; LOW QUALITY PROTEIN: protein naked cuticle homolog 2 [KO:K03213]
112857306  NKD1; protein naked cuticle homolog 1 [KO:K03213]
112861082  TCF7; transcription factor 7 isoform X1 [KO:K02620]
112869689  TCF7L1; transcription factor 7-like 1 [KO:K04490]
112854283  TCF7L2; transcription factor 7-like 2 [KO:K04491]
112858040  LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
112859511  MYC; myc proto-oncogene protein [KO:K04377]
112867915  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
112862913  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
112859371  SNAI2; zinc finger protein SNAI2 [KO:K05706]
112865900  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
112865907  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
112864619  ACTG1; actin, cytoplasmic 2 [KO:K05692]
112860092  ACTB; actin, cytoplasmic 1 [KO:K05692]
112869024  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
112854453  CTNNA3; catenin alpha-3 [KO:K05691]
112861294  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
pcoo04120  Ubiquitin mediated proteolysis
pcoo04310  Wnt signaling pathway
pcoo04350  TGF-beta signaling pathway
pcoo04520  Adherens junction
pcoo04530  Tight junction
KO pathway
ko04390   
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