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GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.
Walker MF, Zhang J, Steiner W, Ku PI, Zhu JF, Michaelson Z, Yen YC, Lee A, Long AB, Casey MJ, Poddar A, Nelson IB, Arveseth CD, Nagel F, Clough R, LaPotin S, Kwan KM, Schulz S, Stewart RA, Tesmer JJG, Caspary T, Subramanian R, Ge X, Myers BR. Walker MF, et al. PLoS Biol. 2024 Aug 13;22(8):e3002685. doi: 10.1371/journal.pbio.3002685. eCollection 2024 Aug. PLoS Biol. 2024. PMID: 39138140 Free PMC article.
Smoothened stimulation by membrane sterols drives Hedgehog pathway activity.
Deshpande I, Liang J, Hedeen D, Roberts KJ, Zhang Y, Ha B, Latorraca NR, Faust B, Dror RO, Beachy PA, Myers BR, Manglik A. Deshpande I, et al. Nature. 2019 Jul;571(7764):284-288. doi: 10.1038/s41586-019-1355-4. Epub 2019 Jul 1. Nature. 2019. PMID: 31263273 Free PMC article.
A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction.
Happ JT, Arveseth CD, Bruystens J, Bertinetti D, Nelson IB, Olivieri C, Zhang J, Hedeen DS, Zhu JF, Capener JL, Bröckel JW, Vu L, King CC, Ruiz-Perez VL, Ge X, Veglia G, Herberg FW, Taylor SS, Myers BR. Happ JT, et al. Nat Struct Mol Biol. 2022 Oct;29(10):990-999. doi: 10.1038/s41594-022-00838-z. Epub 2022 Oct 6. Nat Struct Mol Biol. 2022. PMID: 36202993 Free PMC article.
Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.
Arveseth CD, Happ JT, Hedeen DS, Zhu JF, Capener JL, Klatt Shaw D, Deshpande I, Liang J, Xu J, Stubben SL, Nelson IB, Walker MF, Kawakami K, Inoue A, Krogan NJ, Grunwald DJ, Hüttenhain R, Manglik A, Myers BR. Arveseth CD, et al. PLoS Biol. 2021 Apr 22;19(4):e3001191. doi: 10.1371/journal.pbio.3001191. eCollection 2021 Apr. PLoS Biol. 2021. PMID: 33886552 Free PMC article.
GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade.
Walker MF, Zhang J, Steiner W, Ku PI, Zhu JF, Michaelson Z, Yen YC, Lee A, Long AB, Casey MJ, Poddar A, Nelson IB, Arveseth CD, Nagel F, Clough R, LaPotin S, Kwan KM, Schulz S, Stewart RA, Tesmer JJG, Caspary T, Subramanian R, Ge X, Myers BR. Walker MF, et al. bioRxiv [Preprint]. 2024 Apr 18:2023.05.10.540226. doi: 10.1101/2023.05.10.540226. bioRxiv. 2024. Update in: PLoS Biol. 2024 Aug 13;22(8):e3002685. doi: 10.1371/journal.pbio.3002685 PMID: 37214942 Free PMC article. Updated. Preprint.
A Structural Mechanism for Noncanonical GPCR Signal Transduction in the Hedgehog Pathway.
Steiner WP, Iverson N, Venkatakrishnan V, Wu J, Stepniewski TM, Michaelson Z, Bröckel JW, Zhu JF, Bruystens J, Lee A, Nelson I, Bertinetti D, Arveseth CD, Tan G, Spaltenstein P, Xu J, Hüttenhain R, Kay M, Herberg FW, Selent J, Anand GS, Dunbrack RL Jr, Taylor SS, Myers BR. Steiner WP, et al. bioRxiv [Preprint]. 2024 Nov 1:2024.10.31.621410. doi: 10.1101/2024.10.31.621410. bioRxiv. 2024. PMID: 39554190 Free PMC article. Preprint.