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1998 1
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2010 8
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2014 15
2015 13
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2020 9
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174 results

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Page 1
Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex.
Kwon JJ, Hajian B, Bian Y, Young LC, Amor AJ, Fuller JR, Fraley CV, Sykes AM, So J, Pan J, Baker L, Lee SJ, Wheeler DB, Mayhew DL, Persky NS, Yang X, Root DE, Barsotti AM, Stamford AW, Perry CK, Burgin A, McCormick F, Lemke CT, Hahn WC, Aguirre AJ. Kwon JJ, et al. Nature. 2022 Sep;609(7926):408-415. doi: 10.1038/s41586-022-04928-2. Epub 2022 Jul 13. Nature. 2022. PMID: 35831509 Free PMC article.
SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital RASopathy syndromes(2-5). ...Complex formation is initially mediated by interactions between SHOC2 and PP1C and is stabilized by the …
SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital …
SHOC2 mediates the drug-resistance of triple-negative breast cancer cells to everolimus.
Geng W, Cao M, Dong K, An J, Gao H. Geng W, et al. Cancer Biol Ther. 2023 Dec 31;24(1):2206362. doi: 10.1080/15384047.2023.2206362. Cancer Biol Ther. 2023. PMID: 37170083 Free PMC article.
Our results showed that everolimus activated the Raf-ERK pathway by promoting the interaction between SHOC2 and c-Raf and that knockdown of SHOC2 significantly inhibited the Raf-ERK pathway induced by everolimus. We further demonstrated that SHOC2 expression …
Our results showed that everolimus activated the Raf-ERK pathway by promoting the interaction between SHOC2 and c-Raf and that knockd …
Structure of the MRAS-SHOC2-PP1C phosphatase complex.
Hauseman ZJ, Fodor M, Dhembi A, Viscomi J, Egli D, Bleu M, Katz S, Park E, Jang DM, Porter KA, Meili F, Guo H, Kerr G, Mollé S, Velez-Vega C, Beyer KS, Galli GG, Maira SM, Stams T, Clark K, Eck MJ, Tordella L, Thoma CR, King DA. Hauseman ZJ, et al. Nature. 2022 Sep;609(7926):416-423. doi: 10.1038/s41586-022-05086-1. Epub 2022 Jul 13. Nature. 2022. PMID: 35830882 Free PMC article.
MRAS, SHOC2 and PP1C are mutated in rasopathies-developmental syndromes caused by aberrant MAPK pathway activation(6-14)-and SHOC2 itself has emerged as potential target in receptor tyrosine kinase (RTK)-RAS-driven tumours(15-18). Despite its importance, structural …
MRAS, SHOC2 and PP1C are mutated in rasopathies-developmental syndromes caused by aberrant MAPK pathway activation(6-14)-and SHOC2 …
Structural insights into the role of SHOC2-MRAS-PP1C complex in RAF activation.
Bonsor DA, Simanshu DK. Bonsor DA, et al. FEBS J. 2023 Oct;290(20):4852-4863. doi: 10.1111/febs.16800. Epub 2023 Apr 26. FEBS J. 2023. PMID: 37074066 Review.
RAF activation is a key step for signalling through the mitogen-activated protein kinase (MAPK) pathway. The SHOC2 protein, along with MRAS and PP1C, forms a high affinity, heterotrimeric holoenzyme that activates RAF kinases by dephosphorylating a specific phosphoserine. …
RAF activation is a key step for signalling through the mitogen-activated protein kinase (MAPK) pathway. The SHOC2 protein, along wit …
Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix.
Norcross RG, Abdelmoti L, Rouchka EC, Andreeva K, Tussey O, Landestoy D, Galperin E. Norcross RG, et al. Dev Biol. 2022 Dec;492:156-171. doi: 10.1016/j.ydbio.2022.10.010. Epub 2022 Oct 18. Dev Biol. 2022. PMID: 36265687 Free PMC article.
The extracellular signal-regulated kinase (ERK1/2) pathway is essential in embryonic development. The scaffold protein Shoc2 is a critical modulator of ERK1/2 signals, and mutations in the shoc2 gene lead to the human developmental disease known as Noonan-like syndr …
The extracellular signal-regulated kinase (ERK1/2) pathway is essential in embryonic development. The scaffold protein Shoc2 is a cri …
Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome.
Bonsor DA, Alexander P, Snead K, Hartig N, Drew M, Messing S, Finci LI, Nissley DV, McCormick F, Esposito D, Rodriguez-Viciana P, Stephen AG, Simanshu DK. Bonsor DA, et al. Nat Struct Mol Biol. 2022 Oct;29(10):966-977. doi: 10.1038/s41594-022-00841-4. Epub 2022 Sep 29. Nat Struct Mol Biol. 2022. PMID: 36175670 Free PMC article.
SHOC2 acts as a strong synthetic lethal interactor with MEK inhibitors in multiple KRAS cancer cell lines. ...Here we present the high-resolution crystal structure of the SHOC2-MRAS-PP1C (SMP) complex and apo-SHOC2. Our structures reveal that SHOC2, MR …
SHOC2 acts as a strong synthetic lethal interactor with MEK inhibitors in multiple KRAS cancer cell lines. ...Here we present the hig …
A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective.
Kwon JJ, Hahn WC. Kwon JJ, et al. Mol Cell Biol. 2021 Mar 24;41(4):e00627-20. doi: 10.1128/MCB.00627-20. Print 2021 Mar 24. Mol Cell Biol. 2021. PMID: 33526449 Free PMC article. Review.
Gain-of-function germ line mutations of SHOC2 drive the RASopathy Noonan-like syndrome, and SHOC2 mediates adaptive resistance to mitogen-activated protein kinase (MAPK) inhibitors. ...Here, we review the structural features of SHOC2 that mediate its known fu …
Gain-of-function germ line mutations of SHOC2 drive the RASopathy Noonan-like syndrome, and SHOC2 mediates adaptive resistance …
SHOC2 complex-driven RAF dimerization selectively contributes to ERK pathway dynamics.
Boned Del Río I, Young LC, Sari S, Jones GG, Ringham-Terry B, Hartig N, Rejnowicz E, Lei W, Bhamra A, Surinova S, Rodriguez-Viciana P. Boned Del Río I, et al. Proc Natl Acad Sci U S A. 2019 Jul 2;116(27):13330-13339. doi: 10.1073/pnas.1902658116. Epub 2019 Jun 18. Proc Natl Acad Sci U S A. 2019. PMID: 31213532 Free PMC article.
Heterodimerization of RAF kinases as well as dephosphorylation of a conserved "S259" inhibitory site are important steps for RAF activation but the precise mechanisms and dynamics remain unclear. A ternary complex comprised of SHOC2, MRAS, and PP1 (SHOC2 complex) fu …
Heterodimerization of RAF kinases as well as dephosphorylation of a conserved "S259" inhibitory site are important steps for RAF activation …
SHOC2 Is a Critical Modulator of Sensitivity to EGFR-TKIs in Non-Small Cell Lung Cancer Cells.
Terai H, Hamamoto J, Emoto K, Masuda T, Manabe T, Kuronuma S, Kobayashi K, Masuzawa K, Ikemura S, Nakayama S, Kawada I, Suzuki Y, Takeuchi O, Suzuki Y, Ohtsuki S, Yasuda H, Soejima K, Fukunaga K. Terai H, et al. Mol Cancer Res. 2021 Feb;19(2):317-328. doi: 10.1158/1541-7786.MCR-20-0664. Epub 2020 Oct 26. Mol Cancer Res. 2021. PMID: 33106373
Using a CRISPR/Cas9-based screen, we identified the leucine-rich repeat scaffold protein SHOC2 as a key modulator of sensitivity to EGFR-TKI treatment. On the basis of in vitro assays, we demonstrated that SHOC2 expression levels strongly correlate with the sensitiv …
Using a CRISPR/Cas9-based screen, we identified the leucine-rich repeat scaffold protein SHOC2 as a key modulator of sensitivity to E …
Structural basis for SHOC2 modulation of RAS signalling.
Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J. Liau NPD, et al. Nature. 2022 Sep;609(7926):400-407. doi: 10.1038/s41586-022-04838-3. Epub 2022 Jun 29. Nature. 2022. PMID: 35768504 Free PMC article.
Prior to RAF dimerization, the protein phosphatase 1 catalytic subunit (PP1C) must dephosphorylate the N-terminal phosphoserine (NTpS) of RAF(11) to relieve inhibition by 14-3-3, although PP1C in isolation lacks intrinsic substrate selectivity. SHOC2 is as an essential sca …
Prior to RAF dimerization, the protein phosphatase 1 catalytic subunit (PP1C) must dephosphorylate the N-terminal phosphoserine (NTpS) of RA …
174 results