KEGG   PATHWAY: mmu04390
Entry
mmu04390                    Pathway                                
Name
Hippo signaling pathway - Mus musculus (house mouse)
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
mmu04390  Hippo signaling pathway
mmu04390

Other DBs
GO: 0035329
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
100039786  Gm2423; predicted gene 2423 [KO:K16197]
101543  Wtip; WT1 interacting protein [KO:K16682]
103583  Fbxw11; F-box and WD-40 domain protein 11 [KO:K03362]
104318  Csnk1d; casein kinase 1, delta [KO:K08959] [EC:2.7.11.1]
105782  Scrib; scribbled planar cell polarity [KO:K16175]
11461  Actb; actin, beta [KO:K05692]
11465  Actg1; actin, gamma, cytoplasmic 1 [KO:K05692]
11576  Afp; alpha fetoprotein [KO:K16144]
11705  Amh; anti-Mullerian hormone [KO:K04665]
11789  Apc; APC, WNT signaling pathway regulator [KO:K02085]
11796  Birc3; baculoviral IAP repeat-containing 3 [KO:K16060]
11797  Birc2; baculoviral IAP repeat-containing 2 [KO:K16060]
11799  Birc5; baculoviral IAP repeat-containing 5 [KO:K08731]
11839  Areg; amphiregulin [KO:K09782]
12005  Axin1; axin 1 [KO:K02157]
12006  Axin2; axin 2 [KO:K04385]
12156  Bmp2; bone morphogenetic protein 2 [KO:K21283]
12159  Bmp4; bone morphogenetic protein 4 [KO:K04662]
12160  Bmp5; bone morphogenetic protein 5 [KO:K04663]
12161  Bmp6; bone morphogenetic protein 6 [KO:K16620]
12162  Bmp7; bone morphogenetic protein 7 [KO:K16621]
12163  Bmp8a; bone morphogenetic protein 8a [KO:K16622]
12164  Bmp8b; bone morphogenetic protein 8b [KO:K16622]
12166  Bmpr1a; bone morphogenetic protein receptor, type 1A [KO:K04673] [EC:2.7.11.30]
12167  Bmpr1b; bone morphogenetic protein receptor, type 1B [KO:K13578] [EC:2.7.11.30]
12168  Bmpr2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
12234  Btrc; beta-transducin repeat containing protein [KO:K03362]
12385  Ctnna1; catenin alpha 1 [KO:K05691]
12386  Ctnna2; catenin alpha 2 [KO:K05691]
12387  Ctnnb1; catenin beta 1 [KO:K02105]
12443  Ccnd1; cyclin D1 [KO:K04503]
12444  Ccnd2; cyclin D2 [KO:K10151]
12445  Ccnd3; cyclin D3 [KO:K10152]
12550  Cdh1; cadherin 1 [KO:K05689]
12695  Patj; PATJ, crumbs cell polarity complex component [KO:K06092]
13383  Dlg1; discs large MAGUK scaffold protein 1 [KO:K12076]
13385  Dlg4; discs large MAGUK scaffold protein 4 [KO:K11828]
13542  Dvl1; dishevelled segment polarity protein 1 [KO:K02353]
13543  Dvl2; dishevelled segment polarity protein 2 [KO:K02353]
13544  Dvl3; dishevelled segment polarity protein 3 [KO:K02353]
14164  Fgf1; fibroblast growth factor 1 [KO:K18496]
14219  Ccn2; cellular communication network factor 2 [KO:K06827]
14362  Fzd1; frizzled class receptor 1 [KO:K02432]
14365  Fzd3; frizzled class receptor 3 [KO:K02329]
14366  Fzd4; frizzled class receptor 4 [KO:K02354]
14367  Fzd5; frizzled class receptor 5 [KO:K02375]
14368  Fzd6; frizzled class receptor 6 [KO:K02376]
14369  Fzd7; frizzled class receptor 7 [KO:K02432]
14370  Fzd8; frizzled class receptor 8 [KO:K02375]
14371  Fzd9; frizzled class receptor 9 [KO:K02842]
14563  Gdf5; growth differentiation factor 5 [KO:K04664]
14633  Gli2; GLI-Kruppel family member GLI2 [KO:K16798]
15901  Id1; inhibitor of DNA binding 1, HLH protein [KO:K04680]
15902  Id2; inhibitor of DNA binding 2 [KO:K17693]
16414  Itgb2; integrin beta 2 [KO:K06464]
16415  Itgb2l; integrin beta 2-like [KO:K06464]
16475  Ajuba; ajuba LIM protein [KO:K16682]
16798  Lats1; large tumor suppressor [KO:K08791] [EC:2.7.11.1]
16842  Lef1; lymphoid enhancer binding factor 1 [KO:K04492]
16897  Llgl1; LLGL1 scribble cell polarity complex component [KO:K06094]
170770  Bbc3; BCL2 binding component 3 [KO:K10132]
170788  Crb1; crumbs family member 1, photoreceptor morphogenesis associated [KO:K16681]
17125  Smad1; SMAD family member 1 [KO:K04676]
17126  Smad2; SMAD family member 2 [KO:K04500]
17127  Smad3; SMAD family member 3 [KO:K23605]
17128  Smad4; SMAD family member 4 [KO:K04501]
17131  Smad7; SMAD family member 7 [KO:K19631]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
18016  Nf2; neurofibromin 2 [KO:K16684]
18759  Prkci; protein kinase C, iota [KO:K06069] [EC:2.7.11.13]
18762  Prkcz; protein kinase C, zeta [KO:K18952] [EC:2.7.11.13]
18787  Serpine1; serine (or cysteine) peptidase inhibitor, clade E, member 1 [KO:K03982]
19045  Ppp1ca; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
19046  Ppp1cb; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
19047  Ppp1cc; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
19052  Ppp2ca; protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform [KO:K04382] [EC:3.1.3.16]
19053  Ppp2cb; protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform [KO:K04382] [EC:3.1.3.16]
20583  Snai2; snail family zinc finger 2 [KO:K05706]
20674  Sox2; SRY (sex determining region Y)-box 2 [KO:K16796]
20890  Wnt8a; wingless-type MMTV integration site family, member 8A [KO:K00714]
209456  Trp53bp2; transformation related protein 53 binding protein 2 [KO:K16823]
211652  Wwc1; WW, C2 and coiled-coil domain containing 1 [KO:K16685]
21414  Tcf7; transcription factor 7, T cell specific [KO:K02620]
21415  Tcf7l1; transcription factor 7 like 1 (T cell specific, HMG box) [KO:K04490]
21416  Tcf7l2; transcription factor 7 like 2, T cell specific, HMG box [KO:K04491]
216033  Ctnna3; catenin alpha 3 [KO:K05691]
21676  Tead1; TEA domain family member 1 [KO:K09448]
21677  Tead2; TEA domain family member 2 [KO:K09448]
21678  Tead3; TEA domain family member 3 [KO:K09448]
21679  Tead4; TEA domain family member 4 [KO:K09448]
216795  Wnt9a; wingless-type MMTV integration site family, member 9A [KO:K01064]
217325  Llgl2; LLGL2 scribble cell polarity complex component [KO:K06094]
21803  Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21809  Tgfb3; transforming growth factor, beta 3 [KO:K13377]
21812  Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:2.7.11.30]
21813  Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:2.7.11.30]
22062  Trp73; transformation related protein 73 [KO:K10148]
22408  Wnt1; wingless-type MMTV integration site family, member 1 [KO:K03209]
22409  Wnt10a; wingless-type MMTV integration site family, member 10A [KO:K01357]
22410  Wnt10b; wingless-type MMTV integration site family, member 10B [KO:K01357]
22411  Wnt11; wingless-type MMTV integration site family, member 11 [KO:K01384]
22412  Wnt9b; wingless-type MMTV integration site family, member 9B [KO:K01064]
22413  Wnt2; wingless-type MMTV integration site family, member 2 [KO:K00182]
22414  Wnt2b; wingless-type MMTV integration site family, member 2B [KO:K00182]
22415  Wnt3; wingless-type MMTV integration site family, member 3 [KO:K00312]
22416  Wnt3a; wingless-type MMTV integration site family, member 3A [KO:K00312]
22417  Wnt4; wingless-type MMTV integration site family, member 4 [KO:K00408]
22418  Wnt5a; wingless-type MMTV integration site family, member 5A [KO:K00444]
22419  Wnt5b; wingless-type MMTV integration site family, member 5B [KO:K00444]
22420  Wnt6; wingless-type MMTV integration site family, member 6 [KO:K00445]
22421  Wnt7a; wingless-type MMTV integration site family, member 7A [KO:K00572]
22422  Wnt7b; wingless-type MMTV integration site family, member 7B [KO:K00572]
22423  Wnt8b; wingless-type MMTV integration site family, member 8B [KO:K00714]
22601  Yap1; yes-associated protein 1 [KO:K16687]
22627  Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide [KO:K06630]
22628  Ywhag; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide [KO:K16198]
22629  Ywhah; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide [KO:K16198]
22630  Ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
22631  Ywhaz; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide [KO:K16197]
232157  Mob1a; MOB kinase activator 1A [KO:K06685]
23805  Apc2; APC regulator of WNT signaling pathway 2 [KO:K02085]
238057  Gdf7; growth differentiation factor 7 [KO:K20013]
23859  Dlg2; discs large MAGUK scaffold protein 2 [KO:K12075]
241324  Crb2; crumbs family member 2 [KO:K16681]
242316  Gdf6; growth differentiation factor 6 [KO:K20012]
269643  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
27373  Csnk1e; casein kinase 1, epsilon [KO:K08960] [EC:2.7.11.1]
27494  Amot; angiomotin [KO:K16819]
29806  Limd1; LIM domains containing 1 [KO:K16682]
319710  Frmd6; FERM domain containing 6 [KO:K16822]
434233  Ppp1ccb; protein phosphatase 1 catalytic subunit gamma B [KO:K06269] [EC:3.1.3.16]
50523  Lats2; large tumor suppressor 2 [KO:K08791] [EC:2.7.11.1]
51792  Ppp2r1a; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
52432  Ppp2r2d; protein phosphatase 2, regulatory subunit B, delta [KO:K04354]
53310  Dlg3; discs large MAGUK scaffold protein 3 [KO:K21098]
54401  Ywhab; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide [KO:K16197]
56217  Pals1; protein associated with LIN7 1, MAGUK family member [KO:K06091]
56274  Stk3; serine/threonine kinase 3 [KO:K04412]
56289  Rassf1; Ras association (RalGDS/AF-6) domain family member 1 [KO:K09850]
56513  Pard6a; par-6 family cell polarity regulator alpha [KO:K06093]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
57265  Fzd2; frizzled class receptor 2 [KO:K02235]
58220  Pard6b; par-6 family cell polarity regulator beta [KO:K06093]
64010  Sav1; salvador family WW domain containing 1 [KO:K16686]
68473  Mob1b; MOB kinase activator 1B [KO:K06685]
71228  Dlg5; discs large MAGUK scaffold protein 5 [KO:K24050]
71978  Ppp2r2a; protein phosphatase 2, regulatory subunit B, alpha [KO:K04354]
72293  Nkd2; naked cuticle 2 [KO:K03213]
72930  Ppp2r2b; protein phosphatase 2, regulatory subunit B, beta [KO:K04354]
73246  Rassf6; Ras association (RalGDS/AF-6) domain family member 6 [KO:K09854]
73699  Ppp2r1b; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
93735  Wnt16; wingless-type MMTV integration site family, member 16 [KO:K01558]
93737  Pard6g; par-6 family cell polarity regulator gamma [KO:K06093]
93742  Pard3; par-3 family cell polarity regulator [KO:K04237]
93897  Fzd10; frizzled class receptor 10 [KO:K02842]
93960  Nkd1; naked cuticle 1 [KO:K03213]
97064  Wwtr1; WW domain containing transcription regulator 1 [KO:K16820]
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
mmu04120  Ubiquitin mediated proteolysis
mmu04310  Wnt signaling pathway
mmu04350  TGF-beta signaling pathway
mmu04520  Adherens junction
mmu04530  Tight junction
KO pathway
ko04390   

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