Novel Daple-like protein positively regulates both the Wnt/beta-catenin pathway and the Wnt/JNK pathway in Xenopus.
Wnt signaling pathways are essential in various developmental processes including differentiation, proliferation, cell migration, and cell polarity. Wnt proteins execute their multiple functions by activating distinct intracellular signaling cascades, although the mechanisms underlying this activation are not fully understood. We identified a novel Daple-like protein in Xenopus and named it xDal (Xenopus Daple-like). As with Daple, xDal contains several leucine zipper-like regions (LZLs) and a putative PDZ domain-binding motif, and can interact directly with the dishevelled protein. In contrast to mDaple, injection of xDal mRNA into the dorso-vegetal blastomere does not induce ventralization and acted synergistically with xdsh in secondary axis induction. XDal also induced expression of siamois and xnr-3, suggesting that XDal functions as a positive regulator of the Wnt/beta-catenin pathway. Injection of xDal mRNA into the dorso-animal blastomere, however, induced gastrulation-defective phenotypes in a dose-dependent manner. In addition, xDal inhibited activin-induced elongation of animal caps and enhanced c-jun phosphorylation. Based on these findings, xDal is also thought to function in the Wnt/JNK pathway. Moreover, functional domain analysis with several deletion mutants indicated that xDal requires both a putative PDZ domain-binding motif and at least one LZL for its activity. These findings with xDal will provide new information on the Wnt signaling pathways.
Kobayashi
Hiroki
H
Department of Biological Sciences, Graduate School of Sciences, University of Tokyo, 7-8-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Michiue
Tatsuo
T
Yukita
Akira
A
Danno
Hiroki
H
Sakurai
Kenji
K
Fukui
Akimasa
A
Kikuchi
Akira
A
Asashima
Makoto
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D000072261:Dishevelled Proteins; D047108:Embryonic Development / Q000235:genetics; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C507390:CCDC88C protein, Xenopus; D002352:Carrier Proteins; C000606586:DVL1 protein, Xenopus; C490440:Daple protein, mouse; D000072261:Dishevelled Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D029867:Xenopus Proteins; D048031:JNK Mitogen-Activated Protein Kinases