Wnt signaling Pathway (Archived): Difference between revisions

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#* CTBP1 (Q13363) Canonical Wnt signaling pathway.  
#* CTBP1 (Q13363) Canonical Wnt signaling pathway.  
#* CTBP2 (P56545)
#* CTBP2 (P56545)
#* CUL1 (Q13616) direct ubiquitination of CTNNB1 and participate in Wnt signaling
#* CXXC4 (Q9H2H0) negative regulator of the Wnt signaling pathway via its interaction with DVL1
#* DAAM1 (Q9Y4D1) mediates Wnt-induced Dvl-Rho complex formation
#* DAAM2 (Q86T65)
#* DKK1 (O94907) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
#* DKK2 (Q9UBU2) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
#* DKK4 (Q9UBP4) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
#* DNASE1 (P24855)

Revision as of 09:08, 16 June 2010

Project leaders

Varsha Khodiyar, Suzi Lewis

Justification (Impact and significance)

Wnt proteins form a family of highly conserved secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Insights into the mechanisms of Wnt action have emerged from several systems: genetics in Drosophila and Caenorhabditis elegans; biochemistry in cell culture and ectopic gene expression in Xenopus embryos. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling. As currently understood, Wnt proteins bind to receptors of the Frizzled and LRP families on the cell surface. Through several cytoplasmic relay components, the signal is transduced to beta-catenin, which enters the nucleus and forms a complex with TCF to activate transcription of Wnt target gene (text from [1]

Range of species in which the pathway if found

Species experimentally studied

Possible experts

make sure to represent mammals, but also : fly, zebra fish, other models??

Ontology status

Time frame of the project

  • June - August 2010: Primary annotations
  • November - December 2010: Tree Annotation

Background reading

Wnt receptor
Wnt receptor

Families to annotate

  • Pascale and Paul have reviewed the trees, and there are no obvious problems

Summary: http://amigo-sven.princeton.edu/cgi-bin/amigo/phylotree?mode=index&id=PTHR12027+PTHR11309+PTHR10878+PTHR10845+PTHR10529+PTHR23315

  1. wnt: PTHR12027: 6 distinct subfamilies
    • Secreted signalling proteins, implicated in regulation of cell fate and patterning during embryogenesis.
    • wnt1 (P04628), wnt3 (P56703)
    • wnt2 (P09544), wnt5 (P41221, Q9H1J7)
    • wnt4 (P56705), wnt8 (Q9H1J5, Q93098), wnt9 (O14904, O14905), wnt11 (O96014)
    • wnt6 (Q9Y6F9)
    • wnt7 (O00755, O00755, P56706), wnt16 (Q9UBV4)
    • wnt10 (Q9GZT5, O00744)
  2. frizzled: PTHR11309: 7 distinct subfamilies
    • Transmembrane proteins that are receptors for the Wnt signaling proteins.#* fzd1 (Q9UP38), fzd2 (Q14332), fzd7 (O75084)
    • fzd5 (Q13467), fzd8 (Q9H461)
    • fzd4 (Q9ULV1), fzd9 (O00144), fzd10 (Q9ULW2)
    • fzd3 (Q9NPG1)
    • fzd6 (O60353)
  3. SFRP
    • Proteins that are related to the frizzled protein family in that they also contain the Wnt-binding site, but SFRP family are secreted and not membrane bound.
      • I think we should include these
    • SFRP1 (Q8N474)
    • SFRP2 (Q96HF1)
    • SFRP4 (Q6FHJ7)
    • SFRP5 (Q5T4F7)
  4. Dishevelled: PTHR10878
    • Cytoplasmic phosphoproteins, role in cytoplasmic signal transduction of Wnt signaling pathway.
    • dvl1 (O14640), dvl2 (O14641), dvl3 (Q92997)
  5. dixdc1 (? check this?)
  6. Axin: PTHR10845:AN318
    • Subfamily of the RGS (Regulators of G-protein signaling)
    • Axin1 (O15169),
    • axin2 (Q9Y2T1)
    • Cytoplasmic proteins, negative regulator of Wnt signaling pathway? Regulation of beta-catenin stability.
  7. LRP: PTHR10529
    • Probable co-receptor together with Frizzled for Wnt
    • Rather large family; we probably need to select one or a few subfamilies. Suggest LRP5, LRP6.
    • LRP5 (O75197)
    • LRP6 (O75581)
  8. beta-catenin: PTHR23315 and the subtree to which beta-catenin belongs seems okay
    • CTNNB1 (P35222)
    • CTNNBIP1 (Q9NSA3)
    • Intracellular cytoskeleton, role in structure of adherens junction.
  9. Negative regulator of Wnt signaling, degrades CTNNB1
    • APC (P25054)
    • APC2 (O95996)
  10. Mediates the ubiquitination of CTNNB1 and participates in Wnt signaling
    • BTRC (Q9Y297)
  11. Ubiquitin-mediated degradation of beta-catenin (CTNNB1)
    • CACYBP (Q9HB71)
    • CALCR (P30988)
  12. long-term potentiation and neurotransmitter release
    • CAMK2A (Q9UQM7)
    • CAMK2B (Q13554)
    • CAMK2D (Q13557)
    • CAMK2G (Q13555)
  13. More suspects and players
    • CCL2 P13500
    • CCND1 (P24385)
    • CCND2 (P30279)
    • CCND3 (P30281)
    • CER1 (O95813)
    • CHD8 (Q9HCK8) negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity
    • CHEK2 (O96017)
    • CHP (Q99653)
    • CHP2 (O43745)
    • COL1A1 (P02452)
    • COL1A2 (P08123)
    • CREBBP (Q92793) part of canonical Wnt pathway
    • CSNK1A1 (P48729) Participates in Wnt signaling
    • CSNK1A1L (Q8N752) Participates in Wnt signaling
    • CSNK1E (P49674) Participates in Wnt signaling
    • CSNK2A1 (P68400) Participates in Wnt signaling
    • CSNK2A2 (P19784) Participates in Wnt signaling
    • CSNK2B (P67870) Participates in Wnt signaling
    • CTBP1 (Q13363) Canonical Wnt signaling pathway.
    • CTBP2 (P56545)
    • CUL1 (Q13616) direct ubiquitination of CTNNB1 and participate in Wnt signaling
    • CXXC4 (Q9H2H0) negative regulator of the Wnt signaling pathway via its interaction with DVL1
    • DAAM1 (Q9Y4D1) mediates Wnt-induced Dvl-Rho complex formation
    • DAAM2 (Q86T65)
    • DKK1 (O94907) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
    • DKK2 (Q9UBU2) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
    • DKK4 (Q9UBP4) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
    • DNASE1 (P24855)