Protein tyrosine kinase 7 has a conserved role in Wnt/β-catenin canonical signalling.
The receptor protein tyrosine kinase 7 (PTK7) was recently shown to participate in noncanonical Wnt/planar cell polarity signalling during mouse and frog embryonic development. In this study, we report that PTK7 interacts with β-catenin in a yeast two-hybrid assay and mammalian cells. PTK7-deficient cells exhibit weakened β-catenin/T-cell factor transcriptional activity on Wnt3a stimulation. Furthermore, Xenopus PTK7 is required for the formation of Spemann's organizer and for Siamois promoter activation, events that require β-catenin transcriptional activity. Using epistatic assays, we demonstrate that PTK7 functions upstream from glycogen synthase kinase 3. Taken together, our data reveal a new and conserved role for PTK7 in the Wnt canonical signalling pathway.
Inserm, U891, Centre de Recherche en Cancérologie de Marseille, 27 Boulevard Lei Roure, Marseille F-13009.
Francesca
F
Puppo
Virginie
V
Thomé
Anne-Catherine
AC
Lhoumeau
Marie
M
Cibois
Akanksha
A
Gangar
Frédérique
F
Lembo
Edwige
E
Belotti
Sylvie
S
Marchetto
Patrick
P
Lécine
Thomas
T
Prébet
Michael
M
Sebbagh
Won-Sik
WS
Shin
Seung-Taek
ST
Lee
Laurent
L
Kodjabachian
Jean-Paul
JP
Borg
D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020897:Organizers, Embryonic / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis; D051176:beta Catenin / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D018398:Homeodomain Proteins; C093133:SIA1 protein, Xenopus; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; C487768:PTK7 protein, Xenopus; C096905:PTK7 protein, human; C486452:Ptk7 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D038362:Glycogen Synthase Kinase 3