TY - JOUR
T1 - Wg/Wnt signal can be transmitted through arrow/LRP5,6 and axin independently of Zw3/Gsk3β activity
AU - Tolwinski, Nicholas S.
AU - Wehrli, Marcel
AU - Rives, Anna
AU - Erdeniz, Naz
AU - DiNardo, Stephen
AU - Wieschaus, Eric
N1 - Funding Information:
We thank all the members of the Wieschaus, Schüpbach, and DiNardo labs for helpful discussions. We are grateful to K. Willert and R. Nusse for providing stocks and reagents. We thank R. Hoang, J. Goodliffe, and Y. Ahmed for critical reading of the manuscript, J. Goodhouse for help with confocal microscopy, and R. Samanta for technical assistance. This work was supported by the Howard Hughes Medical Institute and the National Institutes of Health grant PO1CA41086 to E.W., and GM45747 to S.D.N. N.E. was supported by NIH fellowship F32GM20342. N.S.T. was supported by the New Jersey Commission on Cancer Research predoctoral grant, and A.R. by an NSF predoctoral grant.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Activation of the Wnt signaling cascade provides key signals during development and in disease. Here we provide evidence, by designing a Wnt receptor with ligand-independent signaling activity, that physical proximity of Arrow (LRP) to the Wnt receptor Frizzled-2 triggers the intracellular signaling cascade. We have uncovered a branch of the Wnt pathway in which Armadillo activity is regulated concomitantly with the levels of Axin protein. The intracellular pathway bypasses Gsk3β/Zw3, the kinase normally required for controlling β-catenin/Armadillo levels, suggesting that modulated degradation of Armadillo is not required for Wnt signaling. We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo.
AB - Activation of the Wnt signaling cascade provides key signals during development and in disease. Here we provide evidence, by designing a Wnt receptor with ligand-independent signaling activity, that physical proximity of Arrow (LRP) to the Wnt receptor Frizzled-2 triggers the intracellular signaling cascade. We have uncovered a branch of the Wnt pathway in which Armadillo activity is regulated concomitantly with the levels of Axin protein. The intracellular pathway bypasses Gsk3β/Zw3, the kinase normally required for controlling β-catenin/Armadillo levels, suggesting that modulated degradation of Armadillo is not required for Wnt signaling. We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo.
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U2 - 10.1016/S1534-5807(03)00063-7
DO - 10.1016/S1534-5807(03)00063-7
M3 - Article
C2 - 12636921
AN - SCOPUS:0037343952
SN - 1534-5807
VL - 4
SP - 407
EP - 418
JO - Developmental Cell
JF - Developmental Cell
IS - 3
ER -