WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop

Megan J. Agajanian, Matthew P. Walker, Alison D. Axtman, Roberta R. Ruela-de-Sousa, D. Stephen Serafin, Alex D. Rabinowitz, David M. Graham, Meagan B. Ryan, Tigist Tamir, Yuko Nakamichi, Melissa V. Gammons, James M. Bennett, Rafael M. Couñago, David H. Drewry, Jonathan M. Elkins, Carina Gileadi, Opher Gileadi, Paulo H. Godoi, Nirav Kapadia, Susanne MüllerAndré S. Santiago, Fiona J. Sorrell, Carrow I. Wells, Oleg Fedorov, Timothy M. Willson, William J. Zuercher, Michael B. Major

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

WNT signal transduction is essential for normal development and contributes to many human diseases. Agajanian et al. used a kinase gain-of-function screen to show that WNT activates the AAK1 kinase to promote clathrin-mediated endocytosis of the WNT receptor. This work identifies an AAK-driven negative feedback loop that downregulates WNT signaling.

Original languageEnglish
Pages (from-to)79-93.e8
JournalCell Reports
Volume26
Issue number1
DOIs
StatePublished - Jan 2 2019
Externally publishedYes

Keywords

  • AAK1
  • AP2M1
  • LRP6
  • WNT signaling
  • clathrin
  • endocytosis
  • feedback loop
  • gain-of-function screen
  • kinase

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    Agajanian, M. J., Walker, M. P., Axtman, A. D., Ruela-de-Sousa, R. R., Serafin, D. S., Rabinowitz, A. D., Graham, D. M., Ryan, M. B., Tamir, T., Nakamichi, Y., Gammons, M. V., Bennett, J. M., Couñago, R. M., Drewry, D. H., Elkins, J. M., Gileadi, C., Gileadi, O., Godoi, P. H., Kapadia, N., ... Major, M. B. (2019). WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop. Cell Reports, 26(1), 79-93.e8. https://doi.org/10.1016/j.celrep.2018.12.023