KEGG   PATHWAY: ppam04340
Entry
ppam04340                   Pathway                                
Name
Hedgehog signaling pathway - Pteronotus mesoamericanus (Parnell's mustached bat)
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
ppam04340  Hedgehog signaling pathway
ppam04340

Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129061554  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
129061822  SPOPL; speckle-type POZ protein-like [KO:K10523]
129061939  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
129062041  HHIP; hedgehog-interacting protein isoform X1 [KO:K06231]
129062351  HHAT; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678]
129062503  IQCE; IQ domain-containing protein E [KO:K24677]
129063290  CUL1; cullin-1 [KO:K03347]
129063322  GLI3; transcriptional activator GLI3 [KO:K06230]
129063413  SMO; smoothened homolog [KO:K06226]
129064182  CSNK1G1; casein kinase I [KO:K08958] [EC:2.7.11.1]
129065641  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
129066149  MEGF8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
129066481  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
129066556  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
129066695  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
129066710  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
129068523  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129068539  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
129069114  PTCH2; protein patched homolog 2 [KO:K11101]
129069640  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129070217  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
129070971  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
129071477  SHH; sonic hedgehog protein isoform X1 [KO:K11988]
129071738  GLI2; zinc finger protein GLI2 [KO:K16798]
129072330  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
129072755  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
129072991  DISP1; protein dispatched homolog 1 isoform X1 [KO:K24680]
129073328  [KO:K08957] [EC:2.7.11.1]
129073672  BOC; brother of CDO [KO:K20020]
129073887  KIF7; kinesin-like protein KIF7 [KO:K18806]
129074231  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
129076025  GLI1; zinc finger protein GLI1 isoform X1 [KO:K16797]
129076750  MOSMO; modulator of smoothened protein [KO:K23663]
129077129  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
129077143  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
129077678  EVC; evC complex member EVC [KO:K19605]
129077679  EVC2; limbin [KO:K19608]
129077820  CSNK1E; casein kinase I [KO:K08960] [EC:2.7.11.1]
129078237  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
129078401  GAS1; growth arrest-specific protein 1 [KO:K06232]
129078764  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129080125  SPOP; speckle-type POZ protein [KO:K10523]
129080307  CUL3; cullin-3 isoform X1 [KO:K03869]
129080628  IHH; indian hedgehog protein [KO:K11989]
129081483  CSNK1G2; casein kinase I [KO:K08958] [EC:2.7.11.1]
129081741  [KO:K08959] [EC:2.7.11.1]
129081908  GPR161; G-protein coupled receptor 161 [KO:K08439]
129082371  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
129083661  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
129083869  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
129084666  DHH; desert hedgehog protein [KO:K11990]
129086314  CDON; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
129086404  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
129087247  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
129087730  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
Compound
C00575  3',5'-Cyclic AMP
Reference
  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
  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
  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
  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
  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
  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
  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
  Authors
Rohatgi R, Scott MP
  Title
Cell biology. Arrestin' movement in cilia.
  Journal
Science 320:1726-7 (2008)
DOI:10.1126/science.1160448
Reference
  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
  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
  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
  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
  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
  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
ppam04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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