KEGG   PATHWAY: mdo04390
Entry
mdo04390                    Pathway                                
Name
Hippo signaling pathway - Monodelphis domestica (gray short-tailed 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
mdo04390  Hippo signaling pathway
mdo04390

Other DBs
GO: 0035329
Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100018080  CRB2; crumbs 2, cell polarity complex component [KO:K16681]
100026638  CRB1; crumbs 1, cell polarity complex component [KO:K16681]
100022889  PARD3; par-3 family cell polarity regulator [KO:K04237]
100022922  PARD6B; par-6 family cell polarity regulator beta [KO:K06093]
100021195  PARD6A; par-6 family cell polarity regulator alpha [KO:K06093]
100017248  PARD6G; par-6 family cell polarity regulator gamma [KO:K06093]
100020001  protein kinase C zeta type-like [KO:K18952] [EC:2.7.11.13]
100030202  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
100020306  protein kinase C zeta type-like [KO:K18952] [EC:2.7.11.13]
103103873  mucin-16-like [KO:K18952] [EC:2.7.11.13]
100617582  protein kinase C zeta type-like [KO:K18952] [EC:2.7.11.13]
100010646  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
100031754  PATJ; PATJ, crumbs cell polarity complex component [KO:K06092]
100023041  MPP5; membrane palmitoylated protein 5 [KO:K06091]
100011594  AMOT; angiomotin [KO:K16819]
100010658  YAP1; Yes associated protein 1 [KO:K16687]
100012240  WWTR1; WW domain containing transcription regulator 1 [KO:K16820]
100027800  CDH1; cadherin 1 [KO:K05689]
100024330  AJUBA; ajuba LIM protein [KO:K16682]
100011191  WTIP; Wilms tumor 1 interacting protein [KO:K16682]
100029879  LIMD1; LIM domains containing 1 [KO:K16682]
100010877  merlin-like [KO:K16684]
100030761  NF2; neurofibromin 2 [KO:K16684]
100026060  WWC1; WW and C2 domain containing 1 [KO:K16685]
100032645  FRMD1; FERM domain containing 1 [KO:K16821]
100009793  FRMD6; FERM domain containing 6 [KO:K16822]
100010219  SAV1; salvador family WW domain containing protein 1 [KO:K16686]
100030422  serine/threonine-protein kinase 3-like [KO:K04412]
103105479  serine/threonine-protein kinase 3-like [KO:K04412]
100023700  RASSF6; Ras association domain family member 6 [KO:K09854]
100028653  RASSF1; Ras association domain family member 1 [KO:K09850]
100012652  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
100017519  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
100026516  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
100028805  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
100023749  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
100014202  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
100018121  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
100023958  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
100026943  LATS1; large tumor suppressor kinase 1 [KO:K08791] [EC:2.7.11.1]
100018709  LATS2; large tumor suppressor kinase 2 [KO:K08791] [EC:2.7.11.1]
100012951  MOB1A; MOB kinase activator 1A [KO:K06685]
100023134  MOB1B; MOB kinase activator 1B [KO:K06685]
100031298  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
100019898  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
100029055  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
100025256  TP53BP2; tumor protein p53 binding protein 2 [KO:K16823]
100015630  LLGL1; LLGL1, scribble cell polarity complex component [KO:K06094]
100027295  LLGL2; LLGL2, scribble cell polarity complex component [KO:K06094]
100016936  SCRIB; scribbled planar cell polarity protein [KO:K16175]
100017371  DLG1; discs large MAGUK scaffold protein 1 [KO:K12076]
100026349  DLG2; discs large MAGUK scaffold protein 2 [KO:K12075]
100011645  DLG3; discs large MAGUK scaffold protein 3 [KO:K21098]
100016655  DLG4; discs large MAGUK scaffold protein 4 [KO:K11828]
100013720  DLG5; discs large MAGUK scaffold protein 5 [KO:K24050]
100029699  CSNK1D; casein kinase 1 delta [KO:K08959] [EC:2.7.11.1]
100016065  CSNK1E; casein kinase I [KO:K08960] [EC:2.7.11.1]
100029508  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
100031160  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
103106761  TP73; tumor protein p73 [KO:K10148]
100020711  BBC3; BCL2 binding component 3 [KO:K10132]
100020113  TEAD4; TEA domain transcription factor 4 [KO:K09448]
100028466  TEAD3; TEA domain transcription factor 3 [KO:K09448]
100030213  TEAD1; TEA domain transcription factor 1 [KO:K09448]
100031049  CTGF; connective tissue growth factor [KO:K06827]
100011403  GLI2; GLI family zinc finger 2 [KO:K16798]
100023978  AREG; amphiregulin [KO:K09782]
100031079  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
100023616  AFP; alpha fetoprotein [KO:K16144]
100024596  ITGB2; integrin subunit beta 2 [KO:K06464]
100023197  FGF1; fibroblast growth factor 1 [KO:K18496]
100019183  TGFB1; transforming growth factor beta 1 [KO:K13375]
100017548  TGFB2; transforming growth factor beta 2 [KO:K13376]
100017937  TGFB3; transforming growth factor beta 3 [KO:K13377]
100011507  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
100031897  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
100019714  SMAD7; SMAD family member 7 [KO:K19631]
100014493  SMAD2; SMAD family member 2 [KO:K04500]
100018703  SMAD3; SMAD family member 3 [KO:K23605]
100010143  SMAD4; SMAD family member 4 [KO:K04501]
100017921  SERPINE1; serpin family E member 1 [KO:K03982]
100031674  BMP2; bone morphogenetic protein 2 [KO:K21283]
100010652  BMP4; bone morphogenetic protein 4 [KO:K04662]
100014774  BMP5; bone morphogenetic protein 5 [KO:K04663]
100020435  BMP6; bone morphogenetic protein 6 [KO:K16620]
100027751  BMP7; bone morphogenetic protein 7 [KO:K16621]
100031977  BMP8B; bone morphogenetic protein 8B [KO:K16622]
100028734  GDF5; growth differentiation factor 5 [KO:K04664]
100030130  GDF6; growth differentiation factor 6 [KO:K20012]
100016948  GDF7; growth differentiation factor 7 [KO:K20013]
100019515  AMH; anti-Mullerian hormone [KO:K04665]
100026839  BMPR1A; bone morphogenetic protein receptor type 1A [KO:K04673] [EC:2.7.11.30]
100016370  BMPR1B; bone morphogenetic protein receptor type 1B [KO:K13578] [EC:2.7.11.30]
100018765  BMPR2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
100018882  SMAD1; SMAD family member 1 [KO:K04676]
100010733  ID1; inhibitor of DNA binding 1, HLH protein [KO:K04680]
100028188  ID2; inhibitor of DNA binding 2, HLH protein [KO:K17693]
100032741  WNT1; Wnt family member 1 [KO:K03209]
100011991  WNT2; Wnt family member 2 [KO:K00182]
100033140  WNT2B; Wnt family member 2B [KO:K00182]
100024702  WNT3; Wnt family member 3 [KO:K00312]
100025651  WNT3A; Wnt family member 3A [KO:K00312]
100026048  WNT4; Wnt family member 4 [KO:K00408]
100012859  WNT5A; Wnt family member 5A [KO:K00444]
100021212  WNT5B; Wnt family member 5B [KO:K00444]
100010861  WNT6; Wnt family member 6 [KO:K00445]
100014091  WNT7B; Wnt family member 7B [KO:K00572]
100028905  WNT7A; Wnt family member 7A [KO:K00572]
100027787  WNT8B; Wnt family member 8B [KO:K00714]
100024816  WNT8A; Wnt family member 8A [KO:K00714]
100025627  WNT9A; Wnt family member 9A [KO:K01064]
100024657  WNT9B; Wnt family member 9B [KO:K01064]
100010973  WNT10A; Wnt family member 10A [KO:K01357]
100028529  WNT11; Wnt family member 11 [KO:K01384]
100012964  WNT16; Wnt family member 16 [KO:K01558]
100027981  FZD1; frizzled class receptor 1 [KO:K02432]
100019281  FZD7; frizzled class receptor 7 [KO:K02432]
100023490  FZD2; frizzled class receptor 2 [KO:K02235]
100030835  FZD3; frizzled class receptor 3 [KO:K02329]
100025855  FZD4; frizzled class receptor 4 [KO:K02354]
100016198  FZD5; frizzled class receptor 5 [KO:K02375]
100018016  FZD8; frizzled class receptor 8 [KO:K02375]
100023959  FZD6; frizzled class receptor 6 [KO:K02376]
100028967  FZD10; frizzled class receptor 10 [KO:K02842]
100029447  FZD9; frizzled class receptor 9 [KO:K02842]
100010047  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
100022768  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
100617787  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
100030704  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
100024059  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
100032061  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
100012276  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
100016805  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
100029105  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
100012447  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100022896  CTNNB1; catenin beta 1 [KO:K02105]
100013592  APC; APC, WNT signaling pathway regulator [KO:K02085]
100020785  APC2; APC2, WNT signaling pathway regulator [KO:K02085]
100016298  AXIN1; axin 1 [KO:K02157]
100024610  AXIN2; axin 2 [KO:K04385]
100013911  NKD1; naked cuticle homolog 1 [KO:K03213]
100014971  NKD2; naked cuticle homolog 2 [KO:K03213]
100017589  TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
100030368  TCF7L1; transcription factor 7 like 1 [KO:K04490]
100021451  TCF7L2; transcription factor 7 like 2 [KO:K04491]
100011783  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
100032344  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
100013257  CCND1; cyclin D1 [KO:K04503]
100016259  CCND2; cyclin D2 [KO:K10151]
100027538  CCND3; cyclin D3 [KO:K10152]
100014523  SOX2; SRY-box 2 [KO:K16796]
100023459  SNAI2; snail family transcriptional repressor 2 [KO:K05706]
100010782  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100010741  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
100025924  ACTG1; actin gamma 1 [KO:K05692]
100029767  actin, cytoplasmic type 5 [KO:K05692]
100011313  actin, cytoplasmic 1 [KO:K05692]
100016601  actin, cytoplasmic 1-like [KO:K05692]
100020439  actin, cytoplasmic 1-like [KO:K05692]
100024060  actin, cytoplasmic 1-like [KO:K05692]
100028958  actin, cytoplasmic 1-like [KO:K05692]
103096124  actin, cytoplasmic 1-like [KO:K05692]
100011351  ACTB; actin beta [KO:K05692]
100010936  CTNNA3; catenin alpha 3 [KO:K05691]
100019630  CTNNA2; catenin alpha 2 [KO:K05691]
100020276  CTNNA1; catenin alpha 1 [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
mdo04120  Ubiquitin mediated proteolysis
mdo04310  Wnt signaling pathway
mdo04350  TGF-beta signaling pathway
mdo04520  Adherens junction
mdo04530  Tight junction
KO pathway
ko04390   
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