Requirement of Prorenin Receptor and Vacuolar H + -ATPase–Mediated Acidification for Wnt Signaling
Copyright policy )Requirement of Prorenin Receptor and Vacuolar H + -ATPase–Mediated Acidification for Wnt Signaling
Of Wnt, Prorenin Receptor, and V-ATPase The Wnt protein binds to receptors at the cell surface and regulates signaling pathways that control a wide range of critical biological processes from stem cell differentiation to generation of cancer. In a screen for components required for Wnt signaling, Cruciat et al. (p. 459 ) discovered an unexpected partner, the prorenin receptor (PRR). PRR bound to the Wnt receptor proteins Fz8 and LRP6. The PRR protein could interact with the receptors and promote Wnt signaling without its cytoplasmic domain through which it initiates signaling in response to the prorenin protein. Its role in Wnt signaling appears to be rather different. The PRR binds to the vacuolar H + –adenosine triphosphatase (V-ATPase), a proton pump that can influence endocytosis by acidification of vesicles. The V-ATPase was also necessary for phosphorylation of LRP6 and Wnt. Thus, PRR may link the V-ATPase to the Wnt receptor protein LRP6, allowing acidification in the vicinity of the activated receptor, which appears to be necessary for phosphorylation of LRP6 and subsequent signaling.
- German Cancer Research Center Germany
- Heidelberg University Germany
Central Nervous System, Homeodomain Proteins, Vacuolar Proton-Translocating ATPases, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Receptors, Cell Surface, Hydrogen-Ion Concentration, Frizzled Receptors, Cell Line, Mice, Cell Line, Tumor, Low Density Lipoprotein Receptor-Related Protein-6, Animals, Humans, Phosphorylation, RNA, Small Interfering, LDL-Receptor Related Proteins, Body Patterning, Signal Transduction
Central Nervous System, Homeodomain Proteins, Vacuolar Proton-Translocating ATPases, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Receptors, Cell Surface, Hydrogen-Ion Concentration, Frizzled Receptors, Cell Line, Mice, Cell Line, Tumor, Low Density Lipoprotein Receptor-Related Protein-6, Animals, Humans, Phosphorylation, RNA, Small Interfering, LDL-Receptor Related Proteins, Body Patterning, Signal Transduction
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