Entry Name Hippo signaling pathway
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 transductionBRITE hierarchy
Pathway map Other DBs Orthology K00182 WNT2; wingless-type MMTV integration site family, member 2
K00312 WNT3; wingless-type MMTV integration site family, member 3
K00408 WNT4; wingless-type MMTV integration site family, member 4
K00444 WNT5; wingless-type MMTV integration site family, member 5
K00445 WNT6; wingless-type MMTV integration site family, member 6
K00572 WNT7; wingless-type MMTV integration site family, member 7
K00714 WNT8; wingless-type MMTV integration site family, member 8
K01064 WNT9; wingless-type MMTV integration site family, member 9
K01357 WNT10; wingless-type MMTV integration site family, member 10
K01384 WNT11; wingless-type MMTV integration site family, member 11
K01558 WNT16; wingless-type MMTV integration site family, member 16
K02085 APC; adenomatosis polyposis coli protein
K02353 DVL; segment polarity protein dishevelled
K02354 FZD4, fz4, CD344; frizzled 4
K02375 FZD5_8, fz2; frizzled 5/8
K02432 FZD1_7, fz; frizzled 1/7
K02620 TCF7, TCF-1; transcription factor 7
K02842 FZD9_10, CD349_50; frizzled 9/10
K03209 WNT1; wingless-type MMTV integration site family, member 1
K03362 FBXW1_11, BTRC, beta-TRCP; F-box and WD-40 domain protein 1/11
K03456 PPP2R1; serine/threonine-protein phosphatase 2A regulatory subunit A
K03982 SERPINE1, PAI1; plasminogen activator inhibitor 1
K04237 PARD3; partitioning defective protein 3
K04354 PPP2R2; serine/threonine-protein phosphatase 2A regulatory subunit B
K04377 MYC; Myc proto-oncogene protein
K04382 PPP2C; serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16 ]
K04412 STK3, MST2; serine/threonine kinase 3
K04490 TCF7L1; transcription factor 7-like 1
K04491 TCF7L2; transcription factor 7-like 2
K04492 LEF1; lymphoid enhancer-binding factor 1
K04500 SMAD2; mothers against decapentaplegic homolog 2
K04501 SMAD4; mothers against decapentaplegic homolog 4
K04503 CCND1; G1/S-specific cyclin-D1
K04662 BMP4; bone morphogenetic protein 4
K04663 BMP5; bone morphogenetic protein 5
K04664 GDF5; growth differentiation factor 5
K04665 AMH; anti-mullerian hormone
K04673 BMPR1A, ALK3, CD292; bone morphogenetic protein receptor type-1A [EC:2.7.11.30 ]
K04676 SMAD1; mothers against decapentaplegic homolog 1
K04680 ID1; DNA-binding protein inhibitor ID1
K05689 CDH1, CDHE, CD324; cadherin 1, type 1, E-cadherin
K05692 ACTB_G1; actin beta/gamma 1
K06091 MPP5, PALS1; MAGUK p55 subfamily member 5
K06092 INADL, PATJ; InaD-like protein
K06093 PARD6; partitioning defective protein 6
K06094 LLGL; lethal(2) giant larvae protein
K06269 PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16 ]
K06464 ITGB2, CD18; integrin beta 2
K06630 YWHAE; 14-3-3 protein epsilon
K06685 MOB1, Mats; MOB kinase activator 1
K06827 CTGF, CCN2, IGFBP8; connective tissue growth factor (insulin-like growth factor-binding protein 8)
K08731 BIRC5; baculoviral IAP repeat-containing protein 5
K08791 LATS1_2, Wts; serine/threonine-protein kinase LATS1/2 [EC:2.7.11.1 ]
K09448 TEAD; transcriptional enhancer factor
K09850 RASSF1; Ras association domain-containing protein 1
K09854 RASSF6; Ras association domain-containing protein 6
K10132 BBC3, PUMA; Bcl-2-binding component 3
K10148 TP73; tumor protein p73
K10151 CCND2; G1/S-specific cyclin-D2
K10152 CCND3; G1/S-specific cyclin-D3
K11828 DLG4, PSD95; discs large protein 4
K12075 DLG2; discs large protein 2
K12076 DLG1; disks large protein 1
K13375 TGFB1; transforming growth factor beta-1
K13376 TGFB2; transforming growth factor beta-2
K13377 TGFB3; transforming growth factor beta-3
K13578 BMPR1B, ALK6, CDw293; bone morphogenetic protein receptor type-1B [EC:2.7.11.30 ]
K16060 BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K16175 SCRIB; protein scribble
K16197 YWHAB_Q_Z; 14-3-3 protein beta/theta/zeta
K16198 YWHAG_H; 14-3-3 protein gamma/eta
K16620 BMP6; bone morphogenetic protein 6
K16621 BMP7; bone morphogenetic protein 7
K16622 BMP8; bone morphogenetic protein 8
K16682 AJUBA, LIMD1, WTIP; LIM domain-containing protein
K16686 SAV1, Sav; scaffold protein salvador
K16687 YAP1, Yki; transcriptional coactivator YAP1
K16796 SOX2; transcription factor SOX2 (SOX group B)
K16798 GLI2; zinc finger protein GLI2
K16820 WWTR1, TAZ; WW domain-containing transcription regulator protein 1
K16821 FRMD1; FERM domain-containing protein 1
K16822 FRMD6; FERM domain-containing protein 6
K16823 TP53BP2, ASPP2; apoptosis-stimulating of p53 protein 2
K17693 ID2; DNA-binding protein inhibitor ID2
K18496 FGF1; fibroblast growth factor 1
K19631 SMAD7; mothers against decapentaplegic homolog 7
K20012 GDF6; growth differentiation factor 6
K20013 GDF7; growth differentiation factor 7
K21098 DLG3; discs large protein 3
K21283 BMP2; bone morphogenetic protein 2
K23605 SMAD3; mothers against decapentaplegic homolog 3
K24050 DLG5; discs large protein 5
Reference Authors Schroeder MC, Halder G
Title Regulation of the Hippo pathway by cell architecture and mechanical signals.
Journal Reference Authors Zhao B, Tumaneng K, Guan KL
Title The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal.
Journal Reference Authors Mauviel A, Nallet-Staub F, Varelas X
Title Integrating developmental signals: a Hippo in the (path)way.
Journal Reference Authors Zhao B, Li L, Guan KL
Title Hippo signaling at a glance.
Journal Reference Authors Zhao B, Li L, Lei Q, Guan KL
Title The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version.
Journal Reference Authors Tremblay AM, Camargo FD
Title Hippo signaling in mammalian stem cells.
Journal Reference Authors Halder G, Johnson RL
Title Hippo signaling: growth control and beyond.
Journal Reference Authors Ramos A, Camargo FD
Title The Hippo signaling pathway and stem cell biology.
Journal Reference Authors Pan D
Title The hippo signaling pathway in development and cancer.
Journal Reference Authors Bao Y, Hata Y, Ikeda M, Withanage K
Title Mammalian Hippo pathway: from development to cancer and beyond.
Journal Reference Authors Zhao B, Lei QY, Guan KL
Title The Hippo-YAP pathway: new connections between regulation of organ size and cancer.
Journal Reference 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 Reference 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 Reference Authors Badouel C, Garg A, McNeill H
Title Herding Hippos: regulating growth in flies and man.
Journal Reference Authors Buttitta LA, Edgar BA
Title How size is controlled: from Hippos to Yorkies.
Journal Reference Authors Liu AM, Wong KF, Jiang X, Qiao Y, Luk JM
Title Regulators of mammalian Hippo pathway in cancer.
Journal Reference Authors Fausti F, Di Agostino S, Sacconi A, Strano S, Blandino G
Title Hippo and rassf1a Pathways: A Growing Affair.
Journal Reference Authors Halder G, Dupont S, Piccolo S
Title Transduction of mechanical and cytoskeletal cues by YAP and TAZ.
Journal Reference Authors Varelas X, Wrana JL
Title Coordinating developmental signaling: novel roles for the Hippo pathway.
Journal Reference 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 Related ko04120 Ubiquitin mediated proteolysis
