KEGG   PATHWAY: dre04340
Entry
dre04340                    Pathway                                
Name
Hedgehog signaling pathway - Danio rerio (zebrafish)
Description
The Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for transduction of the Hedgehog signal in vertebrates. In Hh's absence, the Ptch receptor localizes to the cilium, where it inhibits Smo activation. Gli proteins are phosphorylated by PKA, CKI and GSK3B and partially degraded into truncated Gli repressor form (GliR) that suppresses Hh target gene transcription in the nucleus. In Hh's presence, Ptch disappears from the cilium, and activated Smo contributes to the translocation of the protein complex Gli, Sufu, Kif7 to ciliary tip, where Gli dissociates from the negative regulator Sufu. The production of Gli activator form (GliA) occurs and the increased nuclear accumulation of GliA results in activation transcription of Hh target genes.
Class
Environmental Information Processing; Signal transduction
Pathway map
dre04340  Hedgehog signaling pathway
dre04340

Organism
Danio rerio (zebrafish) [GN:dre]
Gene
100001615  sufu; suppressor of fused homolog [KO:K06229]
100005514  spop; speckle-type POZ protein [KO:K10523]
100006858  csnk1e; casein kinase I isoform epsilon [KO:K08960] [EC:2.7.11.1]
100007048  bcl2b; apoptosis regulator Bcl-2 [KO:K02161]
100332121  si:ch211-237c6.4; G-protein coupled receptor 161-like [KO:K08439]
100535551  gb:eh551987; uncharacterized protein C16orf52 homolog B [KO:K23663]
101886177  lrp2b; low-density lipoprotein receptor-related protein 2 [KO:K06233]
192307  csnk1a1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
280652  cdon; cell adhesion molecule-related/down-regulated by oncogenes precursor [KO:K20033]
30154  gli2a; zinc finger protein GLI2a [KO:K16798]
30181  ptch2; protein patched homolog 1 [KO:K11101]
30189  ptch1; protein patched homolog 1 [KO:K06225]
30222  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
30225  smo; protein smoothened precursor [KO:K06226]
30269  shha; sonic hedgehog protein precursor [KO:K11988]
30299  ihhb; indian hedgehog B protein precursor [KO:K11989]
30444  shhb; tiggy-winkle hedgehog protein precursor [KO:K11988]
30654  gsk3ba; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
321378  arrb2a; arrestin, beta 2a [KO:K04439]
321695  smurf1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
322106  csnk1da; casein kinase I isoform delta-A [KO:K08959] [EC:2.7.11.1]
323883  cul1a; cullin-1a [KO:K03347]
323898  iqce; IQ domain-containing protein E [KO:K24677]
324655  cul3a; cullin-3a [KO:K03869]
326102  hhip; hedgehog-interacting protein precursor [KO:K06231]
334373  fbxw11a; F-box and WD repeat domain-containing 11-A [KO:K03362]
334628  boc; brother of CDO precursor [KO:K20020]
352930  gli1; zinc finger protein GLI1 [KO:K16797]
368421  gpr161a; G-protein coupled receptor 161 [KO:K08439]
393861  hhatla; hedgehog acyltransferase like, a [KO:K24679]
393998  prkacba; protein kinase, cAMP-dependent, catalytic, beta a [KO:K04345] [EC:2.7.11.11]
394099  arrb2b; arrestin, beta 2b [KO:K04439]
403042  gli3; transcriptional activator GLI3 [KO:K06230]
406533  csnk1db; casein kinase I isoform delta-B [KO:K08959] [EC:2.7.11.1]
406816  cul1b; cullin-1b [KO:K03347]
406825  fbxw11b; F-box and WD repeat domain-containing 11-B [KO:K03362]
415210  efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
445076  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
494092  csnk1g1; casein kinase I isoform gamma-1 [KO:K08958] [EC:2.7.11.1]
503728  scube2; signal peptide, CUB and EGF-like domain-containing protein 2 precursor [KO:K24706]
541318  spopla; speckle-type POZ protein-like A [KO:K10523]
544651  kif7; kinesin-like protein kif7 [KO:K18806]
548610  gli2b; zinc finger protein GLI2b [KO:K16798]
550267  kif3a; kinesin-like protein KIF3A [KO:K10394]
553266  arrb1; beta-arrestin-1 [KO:K04439]
553327  mgrn1b; E3 ubiquitin-protein ligase MGRN1b [KO:K10604] [EC:2.3.2.27]
554152  csnk1g2a; casein kinase I isoform gamma-2 [KO:K08958] [EC:2.7.11.1]
557882  gsk3bb; glycogen synthase kinase 3 beta, genome duplicate b [KO:K03083] [EC:2.7.11.26]
558147  dhh; desert hedgehog protein precursor [KO:K11990]
558170  spoplb; speckle-type POZ protein-like B [KO:K10523]
560334  hhat; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678]
561724  csnk1g2b; casein kinase I isoform gamma-3 isoform 1 [KO:K08958] [EC:2.7.11.1]
563147  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
563633  smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
564064  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a [KO:K04345] [EC:2.7.11.11]
565038  ccnd2b; G1/S-specific cyclin-D2b [KO:K10151]
568184  lrp2a; low-density lipoprotein receptor-related protein 2a precursor [KO:K06233]
569403  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
570772  bcl2a; apoptosis regulator Bcl-2a [KO:K02161]
572370  cul3b; cullin-3b [KO:K03869]
619201  disp1; protein dispatched homolog 1 [KO:K24680]
619520  ihha; Indian hedgehog signaling molecule a precursor [KO:K11989]
767723  mosmob; modulator of smoothened protein precursor [KO:K23663]
777760  gas1b; growth arrest-specific protein 1b [KO:K06232]
791154  megf8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
792224  hhatlb; hedgehog acyltransferase like, b [KO:K24679]
793939  mgrn1a; probable E3 ubiquitin-protein ligase MGRN1 isoform 2 [KO:K10604] [EC:2.3.2.27]
796318  gas1a; growth arrest-specific protein 1a precursor [KO:K06232]
799608  ccnd2a; G1/S-specific cyclin-D2a [KO:K10151]
Compound
C00575  3',5'-Cyclic AMP
Reference
PMID:26875496
  Authors
Xavier GM, Seppala M, Barrell W, Birjandi AA, Geoghegan F, Cobourne MT
  Title
Hedgehog receptor function during craniofacial development.
  Journal
Dev Biol 415:198-215 (2016)
DOI:10.1016/j.ydbio.2016.02.009
Reference
PMID:23719536
  Authors
Briscoe J, Therond PP
  Title
The mechanisms of Hedgehog signalling and its roles in development and disease.
  Journal
Nat Rev Mol Cell Biol 14:416-29 (2013)
DOI:10.1038/nrm3598
Reference
PMID:26077918
  Authors
Alman BA
  Title
The role of hedgehog signalling in skeletal health and disease.
  Journal
Nat Rev Rheumatol 11:552-60 (2015)
DOI:10.1038/nrrheum.2015.84
Reference
PMID:26064136
  Authors
Mooney CJ, Hakimjavadi R, Fitzpatrick E, Kennedy E, Walls D, Morrow D, Redmond EM, Cahill PA
  Title
Hedgehog and Resident Vascular Stem Cell Fate.
  Journal
Stem Cells Int 2015:468428 (2015)
DOI:10.1155/2015/468428
Reference
PMID:23799571
  Authors
Sasai N, Briscoe J
  Title
Primary cilia and graded Sonic Hedgehog signaling.
  Journal
Wiley Interdiscip Rev Dev Biol 1:753-72 (2012)
DOI:10.1002/wdev.43
Reference
PMID:20708941
  Authors
Heretsch P, Tzagkaroulaki L, Giannis A
  Title
Modulators of the hedgehog signaling pathway.
  Journal
Bioorg Med Chem 18:6613-24 (2010)
DOI:10.1016/j.bmc.2010.07.038
Reference
PMID:22534646
  Authors
Anderson E, Peluso S, Lettice LA, Hill RE
  Title
Human limb abnormalities caused by disruption of hedgehog signaling.
  Journal
Trends Genet 28:364-73 (2012)
DOI:10.1016/j.tig.2012.03.012
Reference
PMID:18583599
  Authors
Rohatgi R, Scott MP
  Title
Cell biology. Arrestin' movement in cilia.
  Journal
Science 320:1726-7 (2008)
DOI:10.1126/science.1160448
Reference
PMID:24925320
  Authors
Yue S, Tang LY, Tang Y, Tang Y, Shen QH, Ding J, Chen Y, Zhang Z, Yu TT, Zhang YE, Cheng SY
  Title
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception.
  Journal
Elife 3:e02555 (2014)
DOI:10.7554/eLife.02555
Reference
PMID:22056910
  Authors
Ok CY, Singh RR, Vega F
  Title
Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms.
  Journal
Am J Pathol 180:2-11 (2012)
DOI:10.1016/j.ajpath.2011.09.009
Reference
PMID:26366162
  Authors
Hsia EY, Gui Y, Zheng X
  Title
Regulation of Hedgehog signaling by ubiquitination.
  Journal
Front Biol (Beijing) 10:203-220 (2015)
DOI:10.1007/s11515-015-1343-5
Reference
PMID:29290584
  Authors
Pusapati GV, Kong JH, Patel BB, Krishnan A, Sagner A, Kinnebrew M, Briscoe J, Aravind L, Rohatgi R
  Title
CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.
  Journal
Dev Cell 44:113-129.e8 (2018)
DOI:10.1016/j.devcel.2017.12.003
Reference
PMID:24582806
  Authors
Pusapati GV, Hughes CE, Dorn KV, Zhang D, Sugianto P, Aravind L, Rohatgi R
  Title
EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia.
  Journal
Dev Cell 28:483-96 (2014)
DOI:10.1016/j.devcel.2014.01.021
Reference
PMID:27779865
  Authors
Rodgers UR, Lanyon-Hogg T, Masumoto N, Ritzefeld M, Burke R, Blagg J, Magee AI, Tate EW
  Title
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
  Journal
ACS Chem Biol 11:3256-3262 (2016)
DOI:10.1021/acschembio.6b00896
Related
pathway
dre04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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