KEGG   PATHWAY: rno04390
Entry
rno04390                    Pathway                                
Name
Hippo signaling pathway - Rattus norvegicus (rat)
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
rno04390  Hippo signaling pathway
rno04390

Other DBs
GO: 0035329
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
366031  Crb2; protein crumbs homolog 2 precursor [KO:K16681]
304825  Crb1; protein crumbs homolog 1 precursor [KO:K16681]
81918  Pard3; partitioning defective 3 homolog [KO:K04237]
307237  Pard6g; partitioning defective 6 homolog gamma [KO:K06093]
307799  Pard6a; partitioning defective 6 homolog alpha isoform 1 [KO:K06093]
362279  Pard6b; partitioning defective 6 homolog beta [KO:K06093]
25522  Prkcz; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
84006  Prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
140581  Patj; inaD-like protein [KO:K06092]
314259  Pals1; protein PALS1 [KO:K06091]
300289  Amot; angiomotin isoform X1 [KO:K16819]
295062  Wwtr1; WW domain-containing transcription regulator protein 1 [KO:K16820]
83502  Cdh1; cadherin-1 precursor [KO:K05689]
85265  Ajuba; LIM domain-containing protein ajuba [KO:K16682]
361552  Wtip; Wilms tumor protein 1-interacting protein [KO:K16682]
316101  Limd1; LIM domain-containing protein 1 [KO:K16682]
25744  Nf2; merlin [KO:K16684]
303039  Wwc1; protein KIBRA [KO:K16685]
689709  Frmd1; FERM domain-containing protein 1 [KO:K16821]
257646  Frmd6; FERM domain-containing protein 6 isoform 2 [KO:K16822]
299116  Sav1; protein salvador homolog 1 [KO:K16686]
65189  Stk3; serine/threonine-protein kinase 3 [KO:K04412]
305251  Rassf6; ras association domain-containing protein 6 [KO:K09854]
363140  Rassf1; ras association domain-containing protein 1 isoform 2 [KO:K09850]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100362453  Ppp2cal1; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
246255  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
60660  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform 1 [KO:K04354]
117256  Ppp2r2c; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform isoform 1 [KO:K04354]
117104  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
305922  Lats2; serine/threonine-protein kinase LATS2 [KO:K08791] [EC:2.7.11.1]
308265  Lats1; serine/threonine-protein kinase LATS1 [KO:K08791] [EC:2.7.11.1]
360920  Mob1b; MOB kinase activator 1B [KO:K06685]
297387  Mob1a; MOB kinase activator 1A [KO:K06685]
24668  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
24669  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform 1 [KO:K06269] [EC:3.1.3.16]
25594  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
305025  Tp53bp2; apoptosis-stimulating of p53 protein 2 isoform X1 [KO:K16823]
54265  Llgl1; lethal(2) giant larvae protein homolog 1 [KO:K06094]
360661  Llgl2; LLGL scribble cell polarity complex component 2 [KO:K06094]
362938  Scrib; protein scribble homolog [KO:K16175]
25252  Dlg1; disks large homolog 1 isoform 1 [KO:K12076]
64053  Dlg2; disks large homolog 2 [KO:K12075]
58948  Dlg3; disks large homolog 3 [KO:K21098]
29495  Dlg4; disks large homolog 4 [KO:K11828]
305645  Dlg5; disks large homolog 5 [KO:K24050]
64462  Csnk1d; casein kinase I isoform delta isoform 1 [KO:K08959] [EC:2.7.11.1]
58822  Csnk1e; casein kinase I [KO:K08960] [EC:2.7.11.1]
361765  Btrc; F-box/WD repeat-containing protein 1A [KO:K03362]
303024  Fbxw11; F-box/WD repeat-containing protein 11 isoform 1 [KO:K03362]
362675  Tp73; tumor protein p73 [KO:K10148]
317673  Bbc3; bcl-2-binding component 3 [KO:K10132]
361630  Tead1; transcriptional enhancer factor TEF-1 [KO:K09448]
294299  Tead3; transcriptional enhancer factor TEF-5 [KO:K09448]
683522  Tead4; TEA domain transcription factor 4 [KO:K09448]
308582  Tead2; transcriptional enhancer factor TEF-4 [KO:K09448]
64032  Ccn2; CCN family member 2 precursor [KO:K06827]
304729  Gli2; zinc finger protein GLI2 [KO:K16798]
29183  Areg; amphiregulin preproprotein [KO:K09782]
64041  Birc5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
24177  Afp; alpha-fetoprotein precursor [KO:K16144]
309684  Itgb2; integrin beta-2 precursor [KO:K06464]
25317  Fgf1; fibroblast growth factor 1 [KO:K18496]
59086  Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
81809  Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
25717  Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377]
29591  Tgfbr1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
81810  Tgfbr2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
81516  Smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
29357  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
25631  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
50554  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
24617  Serpine1; plasminogen activator inhibitor 1 precursor [KO:K03982]
29373  Bmp2; bone morphogenetic protein 2 precursor [KO:K21283]
25296  Bmp4; bone morphogenetic protein 4 precursor [KO:K04662]
315824  Bmp5; bone morphogenetic protein 5 precursor [KO:K04663]
25644  Bmp6; bone morphogenetic protein 6 precursor [KO:K16620]
85272  Bmp7; bone morphogenetic protein 7 precursor [KO:K16621]
679119  Bmp8b; bone morphogenetic protein 8B isoform X2 [KO:K16622]
680931  Bmp8a; bone morphogenetic protein 8A precursor [KO:K16622]
252835  Gdf5; growth/differentiation factor 5 preproprotein [KO:K04664]
252834  Gdf6; growth/differentiation factor 6 precursor [KO:K20012]
252833  Gdf7; growth/differentiation factor 7 isoform 2 precursor [KO:K20013]
25378  Amh; muellerian-inhibiting factor precursor [KO:K04665]
81507  Bmpr1a; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:2.7.11.30]
310914  Bmpr1b; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
140590  Bmpr2; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:2.7.11.30]
25671  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
25261  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
25587  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
24881  Wnt1; proto-oncogene Wnt-1 precursor [KO:K03209]
116466  Wnt2b; protein Wnt-2b [KO:K00182]
114487  Wnt2; protein Wnt-2 precursor [KO:K00182]
24882  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
303181  Wnt3a; protein Wnt-3a precursor [KO:K00312]
84426  Wnt4; protein Wnt-4 precursor [KO:K00408]
64566  Wnt5a; protein Wnt-5a precursor [KO:K00444]
282582  Wnt5b; protein Wnt-5b precursor [KO:K00444]
316526  Wnt6; protein Wnt-6 precursor [KO:K00445]
114850  Wnt7a; protein Wnt-7a precursor [KO:K00572]
315196  Wnt7b; protein Wnt-7b isoform 1 [KO:K00572]
291678  Wnt8a; protein Wnt-8a precursor [KO:K00714]
293990  Wnt8b; protein Wnt-8b precursor [KO:K00714]
287357  Wnt9a; protein Wnt-9a precursor [KO:K01064]
303586  Wnt9b; protein Wnt-9b precursor [KO:K01064]
315294  Wnt10b; protein Wnt-10b precursor [KO:K01357]
316527  Wnt10a; protein Wnt-10a precursor [KO:K01357]
140584  Wnt11; protein Wnt-11 [KO:K01384]
500047  Wnt16; protein Wnt-16 precursor [KO:K01558]
58868  Fzd1; frizzled-1 precursor [KO:K02432]
100360552  Fzd7; frizzled-7 precursor [KO:K02432]
64512  Fzd2; frizzled-2 precursor [KO:K02235]
266715  Fzd3; frizzled-3 precursor [KO:K02329]
64558  Fzd4; frizzled-4 precursor [KO:K02354]
317674  Fzd5; frizzled-5 precursor [KO:K02375]
364754  Fzd8; frizzled-8 precursor [KO:K02375]
282581  Fzd6; frizzled-6 precursor [KO:K02376]
266608  Fzd9; frizzled-9 precursor [KO:K02842]
363913  Fzd10; frizzled-10 precursor [KO:K02842]
83721  Dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
303811  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
303251  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
25578  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
56011  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
25577  Ywhaq; 14-3-3 protein theta [KO:K16197]
29753  Ywhae; 14-3-3 protein epsilon [KO:K06630]
25576  Ywhah; 14-3-3 protein eta [KO:K16198]
56010  Ywhag; 14-3-3 protein gamma [KO:K16198]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
24205  Apc; adenomatous polyposis coli protein [KO:K02085]
299611  Apc2; adenomatous polyposis coli protein 2 [KO:K02085]
79257  Axin1; axin-1 [KO:K02157]
29134  Axin2; axin-2 [KO:K04385]
308068  Nkd2; protein naked cuticle homolog 2 [KO:K03213]
364952  Nkd1; protein naked cuticle homolog 1 [KO:K03213]
363595  Tcf7; transcription factor 7 [KO:K02620]
312451  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
679869  Tcf7l2; transcription factor 7-like 2 [KO:K04491]
161452  Lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
24577  Myc; myc proto-oncogene protein [KO:K04377]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
64033  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
25193  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
499593  Sox2; transcription factor SOX-2 [KO:K16796]
25554  Snai2; zinc finger protein SNAI2 [KO:K05706]
60371  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
78971  Birc3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
100361457  Actg1l1; actin, gamma 1 propeptide-like [KO:K05692]
81822  Actb; actin, cytoplasmic 1 [KO:K05692]
287876  Actg1; actin, cytoplasmic 2 [KO:K05692]
120098222  POTE ankyrin domain family member F [KO:K05692]
307505  Ctnna1; catenin alpha-1 [KO:K05691]
297357  Ctnna2; catenin alpha-2 isoform 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
rno04120  Ubiquitin mediated proteolysis
rno04310  Wnt signaling pathway
rno04350  TGF-beta signaling pathway
rno04520  Adherens junction
rno04530  Tight junction
KO pathway
ko04390   

  All links  
Genome (1)   
   KEGG GENOME (1)   
Gene (155)   
   KEGG GENES (155)   
All databases (156)   

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