Please use this identifier to cite or link to this item:
|Title:||An essential role for Grk2 in Hedgehog signalling downstream of Smoothened||Authors:||Zhao, Zhonghua
Lee, Raymond Teck Ho
Pusapati, Ganesh V.
Ingham, Philip William
|Issue Date:||2016||Source:||Zhao, Z., Lee, R. T. H., Pusapati, G. V., Iyu, A., Rohatgi, R., & Ingham, P. W. (2016). An essential role for Grk2 in Hedgehog signalling downstream of Smoothened. EMBO reports, 17(5), 739-752.||Series/Report no.:||EMBO reports||Abstract:||The G-protein-coupled receptor kinase 2 (adrbk2/GRK2) has been implicated in vertebrate Hedgehog (Hh) signalling based on the effects of its transient knock-down in mammalian cells and zebrafish embryos. Here, we show that the response to Hh signalling is effectively abolished in the absence of Grk2 activity. Zebrafish embryos lacking all Grk2 activity are refractory to both Sonic hedgehog (Shh) and oncogenic Smoothened (Smo) activity, but remain responsive to inhibition of cAMP-dependent protein kinase (PKA) activity. Mutation of the kinase domain abrogates the rescuing activity of grk2 mRNA, suggesting that Grk2 acts in a kinase-dependent manner to regulate the response to Hh. Previous studies have suggested that Grk2 potentiates Smo activity by phosphorylating its C-terminal tail (CTT). In the zebrafish embryo, however, phosphomimetic Smo does not display constitutive activity, whereas phospho-null mutants retain activity, implying phosphorylation is neither sufficient nor necessary for Smo function. Since Grk2 rescuing activity requires the integrity of domains essential for its interaction with GPCRs, we speculate that Grk2 may regulate Hh pathway activity by downregulation of a GPCR.||URI:||https://hdl.handle.net/10356/80521
|ISSN:||1469-221X||DOI:||10.15252/embr.201541532||Rights:||© 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
Files in This Item:
|An essential role for Grk2 in Hedgehog signalling downstream of Smoothened.pdf||1.65 MB||Adobe PDF|
checked on Sep 2, 2020
WEB OF SCIENCETM
checked on Oct 17, 2020
checked on Oct 19, 2020
checked on Oct 19, 2020
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.