KEGG   PATHWAY: els04340
els04340                    Pathway                                

Hedgehog signaling pathway - Esox lucius (northern pike)
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.
Environmental Information Processing; Signal transduction
Pathway map
els04340  Hedgehog signaling pathway

Esox lucius (northern pike) [GN:els]
105014106  ptch1; protein patched homolog 1 isoform X1 [KO:K06225]
105022690  ptch2; protein patched homolog 2 [KO:K11101]
105020341  smo; smoothened homolog [KO:K06226]
105016554  gpr161; G-protein coupled receptor 161 [KO:K08439]
105013090  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:]
105008738  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
105029732  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
105019307  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
105027198  csnk1a1; casein kinase I isoform X2 [KO:K08957] [EC:]
105011643  casein kinase I isoform X1 [KO:K08958] [EC:]
105013760  casein kinase I isoform X1 [KO:K08958] [EC:]
105008993  casein kinase I-like isoform X1 [KO:K08958] [EC:]
105018395  csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:]
105021152  casein kinase I isoform X1 [KO:K08959] [EC:]
105031325  casein kinase I [KO:K08959] [EC:]
105025774  csnk1e; casein kinase I [KO:K08960] [EC:]
105025098  casein kinase I-like [KO:K08960] [EC:]
105027876  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
105031009  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
105028311  gli1; LOW QUALITY PROTEIN: zinc finger protein GLI1 [KO:K16797]
105019975  zinc finger protein GLI2 isoform X1 [KO:K16798]
105024675  gli2; zinc finger protein GLI2 [KO:K16798]
105027597  gli3; transcriptional activator GLI3 isoform X2 [KO:K06230]
105007172  sufu; suppressor of fused homolog isoform X1 [KO:K06229]
105016040  kif7; kinesin-like protein KIF7 isoform X1 [KO:K18806]
105020942  hhip; hedgehog-interacting protein [KO:K06231]
105017289  ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
105018279  G1/S-specific cyclin-D1 [KO:K04503]
105018224  ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
105012998  G1/S-specific cyclin-D2-like [KO:K10151]
105020240  G1/S-specific cyclin-D2 [KO:K10151]
105018981  apoptosis regulator Bcl-2 [KO:K02161]
105027305  apoptosis regulator Bcl-2 [KO:K02161]
105022041  cul1; cullin-1 [KO:K03347]
105024245  cullin-1 [KO:K03347]
105029256  F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
105026178  F-box/WD repeat-containing protein 11 isoform X3 [KO:K03362]
105019360  sonic hedgehog protein A [KO:K11988]
105024267  tiggy-winkle hedgehog protein-like [KO:K11988]
105023172  indian hedgehog B protein [KO:K11989]
105027293  indian hedgehog B protein [KO:K11989]
105013551  dhh; desert hedgehog protein [KO:K11990]
105021964  boc; brother of CDO isoform X1 [KO:K20020]
105028514  cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
105007081  gas1; growth arrest-specific protein 1 [KO:K06232]
105015340  growth arrest-specific protein 1-like [KO:K06232]
105029624  growth arrest-specific protein 1-like [KO:K06232]
114833178  growth arrest-specific protein 1-like [KO:K06232]
105022500  lrp2; low-density lipoprotein receptor-related protein 2 isoform X1 [KO:K06233]
105006884  low-density lipoprotein receptor-related protein 2 [KO:K06233]
105026147  uncharacterized protein C16orf52 homolog B [KO:K23663]
105031513  uncharacterized protein C16orf52 homolog B isoform X2 [KO:K23663]
105024272  megf8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
105013383  mgrn1; E3 ubiquitin-protein ligase MGRN1 [KO:K10604] [EC:]
105021636  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:]
105009663  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:]
105013159  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:]
105015221  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:]
105016756  evc; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
105016757  evc2; limbin [KO:K19608]
105027656  arrb2; beta-arrestin-2 isoform X1 [KO:K04439]
105027032  beta-arrestin-1 [KO:K04439]
105023937  arrestin red cell isoform X1 [KO:K04439]
105025907  kif3a; kinesin-like protein KIF3A isoform X1 [KO:K10394]
105011392  cullin-3 isoform X1 [KO:K03869]
105024564  cullin-3 [KO:K03869]
105009930  spopl; speckle-type POZ protein-like [KO:K10523]
105030301  speckle-type POZ protein [KO:K10523]
C00575  3',5'-Cyclic AMP
Xavier GM, Seppala M, Barrell W, Birjandi AA, Geoghegan F, Cobourne MT
Hedgehog receptor function during craniofacial development.
Dev Biol 415:198-215 (2016)
Briscoe J, Therond PP
The mechanisms of Hedgehog signalling and its roles in development and disease.
Nat Rev Mol Cell Biol 14:416-29 (2013)
Alman BA
The role of hedgehog signalling in skeletal health and disease.
Nat Rev Rheumatol 11:552-60 (2015)
Mooney CJ, Hakimjavadi R, Fitzpatrick E, Kennedy E, Walls D, Morrow D, Redmond EM, Cahill PA
Hedgehog and Resident Vascular Stem Cell Fate.
Stem Cells Int 2015:468428 (2015)
Sasai N, Briscoe J
Primary cilia and graded Sonic Hedgehog signaling.
Wiley Interdiscip Rev Dev Biol 1:753-72 (2012)
Heretsch P, Tzagkaroulaki L, Giannis A
Modulators of the hedgehog signaling pathway.
Bioorg Med Chem 18:6613-24 (2010)
Anderson E, Peluso S, Lettice LA, Hill RE
Human limb abnormalities caused by disruption of hedgehog signaling.
Trends Genet 28:364-73 (2012)
Rohatgi R, Scott MP
Cell biology. Arrestin' movement in cilia.
Science 320:1726-7 (2008)
Yue S, Tang LY, Tang Y, Tang Y, Shen QH, Ding J, Chen Y, Zhang Z, Yu TT, Zhang YE, Cheng SY
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception.
Elife 3:e02555 (2014)
Ok CY, Singh RR, Vega F
Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms.
Am J Pathol 180:2-11 (2012)
Hsia EY, Gui Y, Zheng X
Regulation of Hedgehog signaling by ubiquitination.
Front Biol (Beijing) 10:203-220 (2015)
Pusapati GV, Kong JH, Patel BB, Krishnan A, Sagner A, Kinnebrew M, Briscoe J, Aravind L, Rohatgi R
CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.
Dev Cell 44:113-129.e8 (2018)
els04120  Ubiquitin mediated proteolysis
KO pathway

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