Frat is dispensable for canonical Wnt signaling in mammals.
Wnt-signal transduction through beta-catenin is thought to require the inhibition of GSK3 by Frat/GBP. To investigate the role of Frat in mammalian development, we have generated mice with targeted mutations in all three murine Frat homologs. We show that Frat is normally expressed at sites of active Wnt signaling. Surprisingly, Frat-deficient mice do not display gross abnormalities. Moreover, canonical Wnt signaling in primary cells is unaffected by the loss of Frat. These studies show that Frat is not an essential component of the canonical Wnt pathway in higher organisms, despite the strict requirement of Frat/GBP for maternal Wnt signaling in Xenopus.
van Amerongen
Renée
R
Division of Molecular Genetics, Centre of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
Nawijn
Martijn
M
Franca-Koh
Jonathan
J
Zevenhoven
John
J
van der Gulden
Hanneke
H
Jonkers
Jos
J
Berns
Anton
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C491818:Frat1 protein, mouse; C488487:Frat2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C491814:Peg12 protein, mouse; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins