Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions

Zeng, Xin; Huang, He; Tamai, Keiko; Zhang, Xinjun; Harada, Yasuhiro; Yokota, Chika; Almeida, Karla L.; Wang, Jianbo; Doble, Bradley W.; Woodgett, James R.; Wynshaw‐Boris, Anthony; Hsieh, Jen-Chuen; He, Xi

doi:10.1242/dev.013540

Cited by 412 publications

(430 citation statements)

References 59 publications

(113 reference statements)

Supporting

Mentioning

395

Contrasting

Unclassified

Order By: Relevance

“…Binding of Wnt to the Frizzled-LRP5/6 receptor complex induces a conformational change in LRP5/6 such that it becomes an attractive substrate for GSK-3 and CK1 16,17 . Phosphorylation of the co-receptor by these kinases creates a high-affinity binding site for Axin and this leads to dissolution of the destruction complex, although the precise mechanism remains unclear 18 . Therefore, Wnt increases LRP5/6 phosphorylation by GSK-3 and CK1, which leads to lower β-catenin phosphorylation.…”

Section: Redirection Rather Than Inhibitionmentioning

confidence: 99%

When pathways collide: collaboration and connivance among signalling proteins in development

McNeill

Woodgett

2010

Nat Rev Mol Cell Biol

143

106

View full text Add to dashboard Cite

Signal transduction pathways interact at various levels in defining tissue morphology, size and differentiation during development. Understanding of the mechanisms by which these pathways collude has been greatly enhanced by recent insights into how shared components are independently regulated and how the activity of one system is contextualized by others. Traditionally, the components of signalling pathways have been assumed to show pathway fidelity and to act with a high degree of autonomy. However, as illustrated by the Wnt and Hippo pathways, there is increasing evidence that components are often shared between multiple pathways and other components talk to each other through multiple mechanisms.

show abstract

Section: Redirection Rather Than Inhibitionmentioning

confidence: 99%

When pathways collide: collaboration and connivance among signalling proteins in development

McNeill

Woodgett

2010

Nat Rev Mol Cell Biol

143

106

View full text Add to dashboard Cite

show abstract

“…Several works indicate that Wnt-induced phosphorylation of Dvl (p-Dvl) and LRP6 at Ser 1490 (p-LRP6 (S1490)) initiates the Wnt/b-catenin pathway; moreover, Dvl is an important component that controls Wnt-induced LRP6 phosphorylation at Ser 1490 (Hino et al, 2003;Cong and Schweizer LVarmus 2004;Davidson et al, 2005;Zeng et al, 2005Zeng et al, , 2008Klimowski et al, 2006;Bilic et al, 2007). Through its binding to Dvl, WWOX could repress Wnt-induced Dvl and/or LRP6 phosphorylation, thereby inhibiting the Wnt/b-catenin pathway activity.…”

Section: Binding Domainsmentioning

confidence: 99%

Inhibition of the Wnt/β-catenin pathway by the WWOX tumor suppressor protein

et al. 2009

View full text Add to dashboard Cite

The WWOX gene encodes a candidate tumor suppressor protein (WWOX) implicated in a variety of human diseases such as cancer. To better understand the molecular mechanisms of WWOX action, we investigated novel partners of this protein. Using the two-hybrid system and a coimmunoprecipitation assay, we observed a physical association between WWOX and the Dishevelled protein (Dvl) family signaling elements involved in the Wnt/b-catenin pathway. We found that enforced WWOX expression inhibited, and inhibition of endogenous WWOX expression stimulated the transcriptional activity of the Wnt/b-catenin pathway. Inhibition of endogenous WWOX expression also enhanced the effect of Wnt-3a on b-catenin stability. Moreover, we observed the sequestration of Dvl-2 wild type and Dvl-2NESm, a mutated form of Dvl-2 predominantly localized in the nucleus, in the cytoplasm compartment by WWOX. Our results indicate that WWOX is a novel inhibitor of the Wnt/b-catenin pathway. WWOX would act, at least in part, by preventing the nuclear import of the Dvl proteins.

show abstract

“…21 Binding of the axin-GSK-3b complex to phosphorylated LRP6 inhibits GSK-3b activity allowing cytoplasmic b-catenin to stabilize. 36,37 Thus, GSK-3b in the destruction complex promotes b-catenin degradation, whereas GSK-3b-mediated phosphorylation of LRP6 at the plasma membrane in response to Wnt binding to Fz receptors contributes to the stabilization of b-catenin. Taken together, Wnt binds to Fz-LRP5/6 complex and induces Fz recruitment of Dvl, which in turn recruits the axin-GSK-3b complex to the membrane, and thereby promotes LRP5/6 phosphorylation to initiate an active b-catenin signaling.…”

Section: Canonical Wnt Pathwaymentioning

confidence: 99%

Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders

Balakumar

Jagadeesh

2011

Hypertens Res

View full text Add to dashboard Cite

The renin-angiotensin system and Wnt/frizzled receptor signaling pathways are important in the development of essential organs, and their aberrant activation results in cardiovascular and renal pathologies. The (pro)renin receptor ((P)RR)-bound (pro)renin is enzymatically active generating angiotensin-II and activating mitogen-activated protein kinases, leading to cell proliferation and to upregulation of profibrotic genes expression, resulting in end-organ damage. The (P)RR does more than bind to (pro)renin, because it is functionally linked to the vacuolar-H + -ATPase (v-H + -ATPase) that regulates pH of cellular and intracellular vesicles, and to Wnt signaling. This signaling pathway is essential for cell survival, embryonic development and has had a role in various disease states as evidenced by mutation or genetic ablation of the (P)RR gene. This suggests two types of functions of (P)RRs, first one as a receptor for (pro)renin and second one as an accessory subunit of the v-H + -ATPase and a cofactor of the Wnt/Fz receptor complex. This review will discuss both of these functions of (P)RRs thereby giving new perspectives as to the roles of (P)RRs in cardiovascular and renal pathologies.

show abstract

Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions

Cited by 412 publications

References 59 publications

When pathways collide: collaboration and connivance among signalling proteins in development

When pathways collide: collaboration and connivance among signalling proteins in development

Inhibition of the Wnt/β-catenin pathway by the WWOX tumor suppressor protein

Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders

Contact Info

Product

Resources

About