dpr acts as a molecular switch, inhibiting wnt signaling when unphosphorylated, but promoting wnt signaling when phosphorylated by casein kinase iδεdpr充当分子开关,抑制wnt信号时磷酸化,但促进wnt信号由酪蛋白激酶iδε磷酸化.pdfVIP

Dpr Acts as a Molecular Switch, Inhibiting Wnt Signaling when Unphosphorylated, but Promoting Wnt Signaling when Phosphorylated by Casein Kinase Id/e ¤ Evelyn Teran, Aron D. Branscomb , Joni M. Seeling* Department of Biology, City University of New York, Queens College, Flushing, New York, United States of America Abstract The Wnt pathway is a key regulator of development and tumorigenesis. Dpr (Dact/Frodo) influences Wnt signaling in part through the interaction of its PDZ-B domain with Dsh’s PDZ domain. Studies have shown that XDpr1a and its close relative, Frodo, are involved in multiple steps of the Wnt pathway in either inhibitory or activating roles. We found that XDpr1a is phosphorylated by casein kinase Id/e (CKId/e), an activator of Wnt signaling, in the presence of XDsh. Abrogating XDpr1a’s ability to bind XDsh through mutation of XDpr1a’s PDZ-B domain blocks CK1d/e’s phosphorylation of XDpr1a. Conversely, XDsh possessing a mutation in its PDZ domain that is unable to bind XDpr1a does not promote XDpr1a phosphorylation. Phosphorylation of XDpr1a and XDsh by CKId/e decreases their interaction. Moreover, the phosphorylation of XDpr1a by CKId/e not only abrogates XDpr1a’s promotion of b-catenin degradation but blocks b-catenin degradation. Our data suggest that XDpr1a phosphorylation by CKId/e is dependent on the interaction of XDpr1a’s PDZ-B domain with XDsh’s PDZ domain, and that the phosphorylation state of XDpr1a determines whether it inhibits or activates Wnt signaling. Citation: Teran E, Branscomb AD, Seeling JM (2009) Dpr Acts as a Molecular Switch, Inhibiting Wnt Signaling when Unphosphorylated, but Promoting Wnt Signaling when Phosphorylated by Casein Kinase Id/e. PLoS ONE 4(5): e5522. doi:10.1371/journal.pone.0005522 Editor: Wenqing Xu, University of Washington, Unit