KEGG PATHWAY: pleu04340

PATHWAY: pleu04340

Entry

pleu04340                   Pathway

Name

Hedgehog signaling pathway - Peromyscus leucopus (white-footed mouse)

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

pleu04340

Hedgehog signaling pathway

Organism

Peromyscus leucopus (white-footed mouse) [GN:pleu]

Gene

114681933

Kif3a; LOW QUALITY PROTEIN: kinesin-like protein KIF3A [KO:K10394]

114683226

[KO:K10523]

114683476

Fbxw11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]

114684152

Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]

114684308

Grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]

114685366

Megf8; multiple epidermal growth factor-like domains protein 8 isoform X1 [KO:K23664]

114685370

Gli3; transcriptional activator GLI3 isoform X2 [KO:K06230]

114685988

Grk2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]

114686422

[KO:K10523]

114686514

Csnk1g2; casein kinase I [KO:K08958] [EC:2.7.11.1]

114687553

Arrb2; beta-arrestin-2 [KO:K04439]

114688850

[KO:K10523]

114689115

[KO:K10523]

114689305

[KO:K10523]

114689308

[KO:K10523]

114689419

[KO:K10523]

114689766

Shh; sonic hedgehog protein [KO:K11988]

114689934

Gpr161; G-protein coupled receptor 161 [KO:K08439]

114690425

Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]

114691077

Smo; smoothened homolog [KO:K06226]

114691200

Csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]

114692178

Mosmo; modulator of smoothened protein [KO:K23663]

114692748

Spopl; speckle-type POZ protein-like isoform X1 [KO:K10523]

114692909

[KO:K10523]

114693740

Efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]

114694261

[KO:K08960] [EC:2.7.11.1]

114694498

Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]

114694783

Csnk1g3; casein kinase I [KO:K08958] [EC:2.7.11.1]

114694967

Boc; brother of CDO isoform X1 [KO:K20020]

114696170

Kif7; kinesin-like protein KIF7 isoform X4 [KO:K18806]

114696750

Sufu; suppressor of fused homolog isoform X3 [KO:K06229]

114698005

Cul1; cullin-1 [KO:K03347]

114698264

Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]

114698703

Arrb1; beta-arrestin-1 isoform X1 [KO:K04439]

114699768

Cdon; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]

114700236

Gli2; zinc finger protein GLI2 [KO:K16798]

114701440

Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]

114701479

Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]

114701622

[KO:K06231]

114701807

Lrp2; LOW QUALITY PROTEIN: low-density lipoprotein receptor-related protein 2 [KO:K06233]

114702079

Evc; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]

114702080

Evc2; limbin [KO:K19608]

114702406

Hhat; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678]

114702810

Bcl2; apoptosis regulator Bcl-2 [KO:K02161]

114703314

Cul3; cullin-3 isoform X1 [KO:K03869]

114703913

Csnk1d; casein kinase I isoform X3 [KO:K08959] [EC:2.7.11.1]

114704826

Gli1; zinc finger protein GLI1 [KO:K16797]

114705503

Iqce; IQ domain-containing protein E isoform X1 [KO:K24677]

114707394

Csnk1a1; casein kinase I isoform X2 [KO:K08957] [EC:2.7.11.1]

114707571

Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]

114707651

Hhatl; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]

114708125

Btrc; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]

114708424

Ptch1; protein patched homolog 1 isoform X1 [KO:K06225]

114708558

Dhh; desert hedgehog protein [KO:K11990]

114709305

Ihh; indian hedgehog protein [KO:K11989]

114709388

Ptch2; LOW QUALITY PROTEIN: protein patched homolog 2 [KO:K11101]

114709711

Gas1; growth arrest-specific protein 1 [KO:K06232]

114710427

Disp1; protein dispatched homolog 1 [KO:K24680]

114710457

Scube2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]

114710516

[KO:K10523]

114710520

[KO:K10523]

114710630

Mgrn1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]

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

pleu04120

Ubiquitin mediated proteolysis

KO pathway

ko04340

DBGET integrated database retrieval system