KEGG   PATHWAY: hsa04390
Entry
hsa04390                    Pathway                                
Name
Hippo signaling pathway - Homo sapiens (human)
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
hsa04390  Hippo signaling pathway
hsa04390

Drug
D04262  Fostriecin sodium (USAN)
D10969  Pamrevlumab (USAN/INN)
Other DBs
GO: 0035329
Organism
Homo sapiens (human) [GN:hsa]
Gene
10207  PATJ; PATJ crumbs cell polarity complex component [KO:K06092]
102800317  TPTEP2-CSNK1E; TPTEP2-CSNK1E readthrough [KO:K08960] [EC:2.7.11.1]
10297  APC2; APC regulator of WNT signaling pathway 2 [KO:K02085]
10413  YAP1; Yes1 associated transcriptional regulator [KO:K16687]
10971  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
11186  RASSF1; Ras association domain family member 1 [KO:K09850]
11211  FZD10; frizzled class receptor 10 [KO:K02842]
122786  FRMD6; FERM domain containing 6 [KO:K16822]
126374  WTIP; WT1 interacting protein [KO:K16682]
1453  CSNK1D; casein kinase 1 delta [KO:K08959] [EC:2.7.11.1]
1454  CSNK1E; casein kinase 1 epsilon [KO:K08960] [EC:2.7.11.1]
1490  CCN2; cellular communication network factor 2 [KO:K06827]
1495  CTNNA1; catenin alpha 1 [KO:K05691]
1496  CTNNA2; catenin alpha 2 [KO:K05691]
1499  CTNNB1; catenin beta 1 [KO:K02105]
151449  GDF7; growth differentiation factor 7 [KO:K20013]
154796  AMOT; angiomotin [KO:K16819]
166824  RASSF6; Ras association domain family member 6 [KO:K09854]
1739  DLG1; discs large MAGUK scaffold protein 1 [KO:K12076]
174  AFP; alpha fetoprotein [KO:K16144]
1740  DLG2; discs large MAGUK scaffold protein 2 [KO:K12075]
1741  DLG3; discs large MAGUK scaffold protein 3 [KO:K21098]
1742  DLG4; discs large MAGUK scaffold protein 4 [KO:K11828]
1855  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
1856  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1857  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
2246  FGF1; fibroblast growth factor 1 [KO:K18496]
23286  WWC1; WW and C2 domain containing 1 [KO:K16685]
23291  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
23418  CRB1; crumbs cell polarity complex component 1 [KO:K16681]
23513  SCRIB; scribble planar cell polarity protein [KO:K16175]
2535  FZD2; frizzled class receptor 2 [KO:K02235]
25937  WWTR1; WW domain containing transcription regulator 1 [KO:K16820]
26524  LATS2; large tumor suppressor kinase 2 [KO:K08791] [EC:2.7.11.1]
268  AMH; anti-Mullerian hormone [KO:K04665]
27113  BBC3; BCL2 binding component 3 [KO:K10132]
2736  GLI2; GLI family zinc finger 2 [KO:K16798]
286204  CRB2; crumbs cell polarity complex component 2 [KO:K16681]
29119  CTNNA3; catenin alpha 3 [KO:K05691]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
324  APC; APC regulator of WNT signaling pathway [KO:K02085]
329  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
330  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
332  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
3397  ID1; inhibitor of DNA binding 1 [KO:K04680]
3398  ID2; inhibitor of DNA binding 2 [KO:K17693]
353500  BMP8A; bone morphogenetic protein 8a [KO:K16622]
3689  ITGB2; integrin subunit beta 2 [KO:K06464]
374  AREG; amphiregulin [KO:K09782]
392255  GDF6; growth differentiation factor 6 [KO:K20012]
3993  LLGL2; LLGL scribble cell polarity complex component 2 [KO:K06094]
3996  LLGL1; LLGL scribble cell polarity complex component 1 [KO:K06094]
4086  SMAD1; SMAD family member 1 [KO:K04676]
4087  SMAD2; SMAD family member 2 [KO:K04500]
4088  SMAD3; SMAD family member 3 [KO:K23605]
4089  SMAD4; SMAD family member 4 [KO:K04501]
4092  SMAD7; SMAD family member 7 [KO:K19631]
4609  MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377]
4771  NF2; NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [KO:K16684]
5054  SERPINE1; serpin family E member 1 [KO:K03982]
50855  PARD6A; par-6 family cell polarity regulator alpha [KO:K06093]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
51384  WNT16; Wnt family member 16 [KO:K01558]
54361  WNT4; Wnt family member 4 [KO:K00408]
5499  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
5500  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
5501  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
5515  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
5516  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
5518  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
5519  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
5520  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
5521  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
5522  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
55233  MOB1A; MOB kinase activator 1A [KO:K06685]
5584  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
55844  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
5590  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
56288  PARD3; par-3 family cell polarity regulator [KO:K04237]
595  CCND1; cyclin D1 [KO:K04503]
60  ACTB; actin beta [KO:K05692]
60485  SAV1; salvador family WW domain containing protein 1 [KO:K16686]
64398  PALS1; protein associated with LIN7 1, MAGUK p55 family member [KO:K06091]
650  BMP2; bone morphogenetic protein 2 [KO:K21283]
652  BMP4; bone morphogenetic protein 4 [KO:K04662]
653  BMP5; bone morphogenetic protein 5 [KO:K04663]
654  BMP6; bone morphogenetic protein 6 [KO:K16620]
655  BMP7; bone morphogenetic protein 7 [KO:K16621]
656  BMP8B; bone morphogenetic protein 8b [KO:K16622]
657  BMPR1A; bone morphogenetic protein receptor type 1A [KO:K04673] [EC:2.7.11.30]
658  BMPR1B; bone morphogenetic protein receptor type 1B [KO:K13578] [EC:2.7.11.30]
659  BMPR2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
6591  SNAI2; snail family transcriptional repressor 2 [KO:K05706]
6657  SOX2; SRY-box transcription factor 2 [KO:K16796]
6788  STK3; serine/threonine kinase 3 [KO:K04412]
6932  TCF7; transcription factor 7 [KO:K02620]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
7003  TEAD1; TEA domain transcription factor 1 [KO:K09448]
7004  TEAD4; TEA domain transcription factor 4 [KO:K09448]
7005  TEAD3; TEA domain transcription factor 3 [KO:K09448]
7040  TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  TGFB3; transforming growth factor beta 3 [KO:K13377]
7046  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
7048  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
71  ACTG1; actin gamma 1 [KO:K05692]
7159  TP53BP2; tumor protein p53 binding protein 2 [KO:K16823]
7161  TP73; tumor protein p73 [KO:K10148]
7471  WNT1; Wnt family member 1 [KO:K03209]
7472  WNT2; Wnt family member 2 [KO:K00182]
7473  WNT3; Wnt family member 3 [KO:K00312]
7474  WNT5A; Wnt family member 5A [KO:K00444]
7475  WNT6; Wnt family member 6 [KO:K00445]
7476  WNT7A; Wnt family member 7A [KO:K00572]
7477  WNT7B; Wnt family member 7B [KO:K00572]
7478  WNT8A; Wnt family member 8A [KO:K00714]
7479  WNT8B; Wnt family member 8B [KO:K00714]
7480  WNT10B; Wnt family member 10B [KO:K01357]
7481  WNT11; Wnt family member 11 [KO:K01384]
7482  WNT2B; Wnt family member 2B [KO:K00182]
7483  WNT9A; Wnt family member 9A [KO:K01064]
7484  WNT9B; Wnt family member 9B [KO:K01064]
7529  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
7531  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
7532  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
7533  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
7534  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
7855  FZD5; frizzled class receptor 5 [KO:K02375]
7976  FZD3; frizzled class receptor 3 [KO:K02329]
79981  FRMD1; FERM domain containing 1 [KO:K16821]
80326  WNT10A; Wnt family member 10A [KO:K01357]
81029  WNT5B; Wnt family member 5B [KO:K00444]
8200  GDF5; growth differentiation factor 5 [KO:K04664]
8312  AXIN1; axin 1 [KO:K02157]
8313  AXIN2; axin 2 [KO:K04385]
8321  FZD1; frizzled class receptor 1 [KO:K02432]
8322  FZD4; frizzled class receptor 4 [KO:K02354]
8323  FZD6; frizzled class receptor 6 [KO:K02376]
8324  FZD7; frizzled class receptor 7 [KO:K02432]
8325  FZD8; frizzled class receptor 8 [KO:K02375]
8326  FZD9; frizzled class receptor 9 [KO:K02842]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
84552  PARD6G; par-6 family cell polarity regulator gamma [KO:K06093]
84612  PARD6B; par-6 family cell polarity regulator beta [KO:K06093]
8463  TEAD2; TEA domain transcription factor 2 [KO:K09448]
84962  AJUBA; ajuba LIM protein [KO:K16682]
85407  NKD1; NKD inhibitor of WNT signaling pathway 1 [KO:K03213]
85409  NKD2; NKD inhibitor of WNT signaling pathway 2 [KO:K03213]
894  CCND2; cyclin D2 [KO:K10151]
8945  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
896  CCND3; cyclin D3 [KO:K10152]
89780  WNT3A; Wnt family member 3A [KO:K00312]
8994  LIMD1; LIM domain containing 1 [KO:K16682]
9113  LATS1; large tumor suppressor kinase 1 [KO:K08791] [EC:2.7.11.1]
9231  DLG5; discs large MAGUK scaffold protein 5 [KO:K24050]
92597  MOB1B; MOB kinase activator 1B [KO:K06685]
999  CDH1; cadherin 1 [KO:K05689]
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
hsa04120  Ubiquitin mediated proteolysis
hsa04310  Wnt signaling pathway
hsa04350  TGF-beta signaling pathway
hsa04520  Adherens junction
hsa04530  Tight junction
KO pathway
ko04390   

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