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PMID:17027228

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Citation

Bryja, V, Schulte, G and Arenas, E (2007) Wnt-3a utilizes a novel low dose and rapid pathway that does not require casein kinase 1-mediated phosphorylation of Dvl to activate beta-catenin. Cell. Signal. 19:610-6

Abstract

The current view of canonical Wnt signalling is that following Wnt binding to its receptors (Frizzled-Lrp5/6), dishevelled (Dvl) becomes hyperphosphorylated, and the signal is transduced to the APC-GSK3beta-axin-beta-catenin multiprotein complex, which subsequently dissociates. As a result beta-catenin is not phosphorylated, escapes proteosomal degradation and activates its target genes after translocation to the nucleus. Here, we analyzed the importance of the Wnt-3a-induced phosphorylation and shift in electrophoretic migration of Dvl (PS-Dvl) for the activation of beta-catenin. Analysis of Wnt-3a time- and dose-responses in a dopaminergic cell line showed that beta-catenin is activated rapidly (within minutes) and at a low dose of Wnt-3a (1 ng/ml). Surprisingly, PS-Dvl appeared only after 30 min and at greater doses (> or =20 ng/ml) of Wnt-3a. Moreover, we found that a casein kinase 1 inhibitor (D4476) or siRNA for casein kinase 1 delta/epsilon (CK1delta/epsilon) blocked the Wnt-3a-induced PS-Dvl. Interestingly, CK1 inhibition or siRNA for CK1delta/epsilon did not ablate the activation of beta-catenin by Wnt-3a, indicating that there is a PS-Dvl-independent path to activate beta-catenin. The increase in beta-catenin activation by Wnt-3a (PS-Dvl-dependent or -independent) were blocked by Dickkopf1 (Dkk1), suggesting that the effect of Wnt-3a is in both cases mediated by Lrp5/6 receptors. Thus, our results show that Wnt-3a rapidly induce a partial activation of beta-catenin in the absence of PS-Dvl at low doses, while at high doses induce a full activation of beta-catenin in a PS-Dvl-dependent manner.

Links

PubMed Online version:10.1016/j.cellsig.2006.08.011

Keywords

Adaptor Proteins, Signal Transducing/metabolism; Animals; Blotting, Western; Casein Kinase I/metabolism; Cell Line; Dishevelled Proteins; Dose-Response Relationship, Drug; Kinetics; Phosphoproteins/metabolism; Phosphorylation; RNA Interference; RNA, Small Interfering/metabolism; Rats; Transfection; Wnt Proteins/pharmacology; Wnt3 Protein; beta Catenin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DKK1

involved_in

GO:0090090: negative regulation of canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT3A

involved_in

GO:0001934: positive regulation of protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

  • part_of:(GO:0060070)
  • has_input:(UniProtKB:P51141)
  • occurs_in:(CL:0000700)|part_of(GO:0060070)
  • has_input:(UniProtKB:Q60838)
  • occurs_in:(CL:0000700)|part_of(GO:0060070)
  • has_input:(UniProtKB:Q61062)
  • occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:WNT3A

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:KC1D

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P27467,UniProtKB:Q9JMK2

P

  • occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:KC1E

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P27467,UniProtKB:Q9DC28

P

  • occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:KC1E

involved_in

GO:0006468: protein phosphorylation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9DC28

P

  • has_input:(UniProtKB:Q60838)
  • part_of:(GO:0030177)
  • occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:KC1D

involved_in

GO:0006468: protein phosphorylation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9JMK2

P

  • has_input:(UniProtKB:Q60838)
  • part_of:(GO:0030177)
  • occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:KC1D

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P27467,UniProtKB:Q9JMK2

P

occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:WNT3A

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0000700)

Seeded From UniProt

complete

MOUSE:WNT3A

involved_in

GO:0001934: positive regulation of protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

  • part_of:(GO:0060070)
  • has_regulation_target:(UniProtKB:P51141)
  • occurs_in:(CL:0000700)|part_of(GO:0060070)
  • has_regulation_target:(UniProtKB:Q60838)
  • occurs_in:(CL:0000700)|part_of(GO:0060070)
  • has_regulation_target:(UniProtKB:Q61062)
  • occurs_in:(CL:0000700)

Seeded From UniProt

complete

Notes

See also

References

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