New insights into the mechanism of Wnt signaling pathway activation.
Wnts compromise a large family of secreted, hydrophobic glycoproteins that control a variety of developmental and adult processes in all metazoan organisms. Recent advances in the Wnt-signal studies have revealed that distinct Wnts activate multiple intracellular cascades that regulate cellular proliferation, differentiation, migration, and polarity. Although the mechanism by which Wnts regulate different pathways selectively remains to be clarified, evidence has accumulated that in addition to the formation of ligand-receptor pairs, phosphorylation of receptors, receptor-mediated endocytosis, acidification, and the presence of cofactors, such as heparan sulfate proteoglycans, are also involved in the activation of specific Wnt pathways. Here, we review the mechanism of activation in Wnt signaling initiated on the cell-surface membrane. In addition, the mechanisms for fine-tuning by cross talk between Wnt and other signaling are also discussed.
Department of Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan.
Akira
A
Kikuchi
Hideki
H
Yamamoto
Akira
A
Sato
Shinji
S
Matsumoto
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D008024:Ligands; D016328:NF-kappa B; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin; D058570:TOR Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases