KEGG   PATHWAY: kmr04340
Entry
kmr04340                    Pathway                                
Name
Hedgehog signaling pathway - Kryptolebias marmoratus (mangrove rivulus)
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
kmr04340  Hedgehog signaling pathway
kmr04340

Organism
Kryptolebias marmoratus (mangrove rivulus) [GN:kmr]
Gene
108244808  ptch1; protein patched homolog 1 [KO:K06225]
108239668  ptch2; protein patched homolog 1 [KO:K11101]
108235028  smo; smoothened homolog [KO:K06226]
108232386  gpr161a; G-protein coupled receptor 161 isoform X1 [KO:K08439]
108239664  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
108241350  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X2 [KO:K04345] [EC:2.7.11.11]
108234385  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
108241499  prkacab; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
108251427  csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
108234745  csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
108238442  csnk1g2b; casein kinase I isoform X2 [KO:K08958] [EC:2.7.11.1]
108249450  csnk1da; casein kinase I [KO:K08959] [EC:2.7.11.1]
108236195  casein kinase I [KO:K08960] [EC:2.7.11.1]
108235881  csnk1e; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
108232478  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
108231676  gli1; zinc finger protein GLI1 isoform X1 [KO:K16797]
108228619  zinc finger protein GLI2-like [KO:K16798]
108249764  gli2a; zinc finger protein GLI2a isoform X2 [KO:K16798]
108230452  gli3; transcriptional activator GLI3 [KO:K06230]
108233944  sufu; suppressor of fused homolog isoform X1 [KO:K06229]
108250069  kif7; kinesin-like protein kif7 [KO:K18806]
108231437  hedgehog-interacting protein [KO:K06231]
108237918  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
108237544  ccnd2a; G1/S-specific cyclin-D2a [KO:K10151]
108233174  G1/S-specific cyclin-D2-like [KO:K10151]
108237745  ccndx; cyclin Dx [KO:K10151]
108239676  bcl2b; apoptosis regulator Bcl-2 [KO:K02161]
108229311  apoptosis regulator Bcl-2 [KO:K02161]
108249552  cullin-1 [KO:K03347]
108242388  fbxw11a; F-box/WD repeat-containing protein 11a isoform X2 [KO:K03362]
108243491  hhat; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678] [EC:2.3.1.-]
108238572  hhatla; hedgehog acyltransferase like, a [KO:K24679]
108230339  hhatlb; hedgehog acyltransferase like, b isoform X1 [KO:K24679]
108230333  shha; sonic hedgehog protein A [KO:K11988]
108240386  ihha; indian hedgehog signaling molecule a [KO:K11989]
108235303  dhh; desert hedgehog protein [KO:K11990]
108245467  disp1; protein dispatched homolog 1 [KO:K24680]
108229630  scube2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
108230456  boc; brother of CDO isoform X4 [KO:K20020]
108248802  cdon; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
108233664  gas1a; growth arrest-specific protein 1a [KO:K06232]
108243314  growth arrest-specific protein 1 [KO:K06232]
108248874  lrp2b; low-density lipoprotein receptor-related protein 2 [KO:K06233]
108240755  lrp2a; low-density lipoprotein receptor-related protein 2a isoform X2 [KO:K06233]
108237151  uncharacterized protein C16orf52 homolog A isoform X1 [KO:K23663]
108239272  mosmoa; uncharacterized protein C16orf52 homolog B [KO:K23663]
108235514  megf8; multiple epidermal growth factor-like domains protein 8 isoform X1 [KO:K23664]
108243738  mgrn1b; E3 ubiquitin-protein ligase MGRN1b isoform X1 [KO:K10604] [EC:2.3.2.27]
108247228  E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
108236247  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
108236134  smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
108245400  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
108239827  ellis-van Creveld syndrome protein [KO:K19605]
108239896  limbin [KO:K19608]
108238384  efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
108242488  iqce; IQ domain-containing protein E [KO:K24677]
108250682  arrestin red cell isoform X3 [KO:K04439]
108228275  arrb1; beta-arrestin-1 isoform X1 [KO:K04439]
108240600  kif3a; kinesin-like protein KIF3A isoform X1 [KO:K10394]
108245539  cullin-3 [KO:K03869]
108240497  cul3b; cullin-3b [KO:K03869]
108238559  spopla; speckle-type POZ protein-like A [KO:K10523]
108249912  spop; speckle-type POZ protein [KO:K10523]
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
kmr04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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