{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T07:44:05Z","timestamp":1794037445807,"version":"4.8.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1038\/s41594-022-00841-4","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T12:08:39Z","timestamp":1664453319000},"page":"966-977","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Structure of the SHOC2\u2013MRAS\u2013PP1C complex provides insights into RAF activation and Noonan syndrome"],"prefix":"10.1038","volume":"29","author":[{"given":"Daniel A.","family":"Bonsor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Snead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Hartig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Drew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Messing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo I.","family":"Finci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7523-116X","authenticated-orcid":false,"given":"Dwight V.","family":"Nissley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6619-7120","authenticated-orcid":false,"given":"Frank","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-1687","authenticated-orcid":false,"given":"Dominic","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Rodriguez-Viciana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8259-621X","authenticated-orcid":false,"given":"Andrew G.","family":"Stephen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-4618","authenticated-orcid":false,"given":"Dhirendra K.","family":"Simanshu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"841_CR1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2017.06.009","volume":"170","author":"DK Simanshu","year":"2017","unstructured":"Simanshu, D. K., Nissley, D. V. & McCormick, F. RAS proteins and their regulators in human disease. Cell 170, 17\u201333 (2017).","journal-title":"Cell"},{"key":"841_CR2","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1158\/2159-8290.CD-18-1321","volume":"9","author":"R Yaeger","year":"2019","unstructured":"Yaeger, R. & Corcoran, R. B. Targeting alterations in the RAF\u2013MEK pathway. Cancer Discov. 9, 329\u2013341 (2019).","journal-title":"Cancer Discov."},{"key":"841_CR3","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/bs.acr.2021.07.007","volume":"153","author":"JF Longo","year":"2022","unstructured":"Longo, J. F. & Carroll, S. L. The RASopathies: biology, genetics and therapeutic options. Adv. Cancer Res 153, 305\u2013341 (2022).","journal-title":"Adv. Cancer Res"},{"key":"841_CR4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/nrm3979","volume":"16","author":"H Lavoie","year":"2015","unstructured":"Lavoie, H. & Therrien, M. Regulation of RAF protein kinases in ERK signalling. Nat. Rev. Mol. Cell Biol. 16, 281\u2013298 (2015).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"841_CR5","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/s41586-019-1660-y","volume":"575","author":"E Park","year":"2019","unstructured":"Park, E. et al. Architecture of autoinhibited and active BRAF\u2013MEK1\u201314-3-3 complexes. Nature 575, 545\u2013550 (2019).","journal-title":"Nature"},{"key":"841_CR6","doi-asserted-by":"crossref","unstructured":"Simanshu, D. K. & Morrison, D. K. A structure is worth a thousand words: new insights for RAS and RAF regulation. Cancer Discov. 12, 899\u2013912 (2022).","DOI":"10.1158\/2159-8290.CD-21-1494"},{"key":"841_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21422-x","volume":"12","author":"TH Tran","year":"2021","unstructured":"Tran, T. H. et al. KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation. Nat. Commun. 12, 1176 (2021).","journal-title":"Nat. Commun."},{"key":"841_CR8","doi-asserted-by":"publisher","first-page":"996","DOI":"10.3390\/biom11070996","volume":"11","author":"T Cookis","year":"2021","unstructured":"Cookis, T. & Mattos, C. Crystal structure reveals the full Ras\u2013Raf interface and advances mechanistic understanding of Raf activation. Biomolecules 11, 996 (2021).","journal-title":"Biomolecules"},{"key":"841_CR9","doi-asserted-by":"publisher","first-page":"4698","DOI":"10.1128\/MCB.01636-09","volume":"30","author":"M Molzan","year":"2010","unstructured":"Molzan, M. et al. Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling. Mol. Cell. Biol. 30, 4698\u20134711 (2010).","journal-title":"Mol. Cell. Biol."},{"key":"841_CR10","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.molcel.2006.03.027","volume":"22","author":"P Rodriguez-Viciana","year":"2006","unstructured":"Rodriguez-Viciana, P., Oses-Prieto, J., Burlingame, A., Fried, M. & McCormick, F. A phosphatase holoenzyme comprised of Shoc2\/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity. Mol. Cell 22, 217\u2013230 (2006).","journal-title":"Mol. Cell"},{"key":"841_CR11","doi-asserted-by":"publisher","first-page":"E10576","DOI":"10.1073\/pnas.1720352115","volume":"115","author":"LC Young","year":"2018","unstructured":"Young, L. C. et al. SHOC2\u2013MRAS\u2013PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis. Proc. Natl Acad. Sci. USA 115, E10576\u2013E10585 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"841_CR12","doi-asserted-by":"publisher","first-page":"e66067","DOI":"10.1371\/journal.pone.0066067","volume":"8","author":"M Jeoung","year":"2013","unstructured":"Jeoung, M., Abdelmoti, L., Jang, E. R., Vander Kooi, C. W. & Galperin, E. Functional integration of the conserved domains of Shoc2 scaffold. PLoS ONE 8, e66067 (2013).","journal-title":"PLoS ONE"},{"key":"841_CR13","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1038\/ng.425","volume":"41","author":"V Cordeddu","year":"2009","unstructured":"Cordeddu, V. et al. Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair. Nat. Genet. 41, 1022\u20131026 (2009).","journal-title":"Nat. Genet."},{"key":"841_CR14","first-page":"1290","volume":"35","author":"V Hannig","year":"2014","unstructured":"Hannig, V., Jeoung, M., Jang, E. R., Phillips, J. A. 3rd & Galperin, E. A novel SHOC2 variant in rasopathy. Hum. Mutat. 35, 1290\u20131294 (2014).","journal-title":"Hum. Mutat."},{"key":"841_CR15","first-page":"1046","volume":"40","author":"M Motta","year":"2019","unstructured":"Motta, M. et al. Clinical and functional characterization of a novel RASopathy-causing SHOC2 mutation associated with prenatal-onset hypertrophic cardiomyopathy. Hum. Mutat. 40, 1046\u20131056 (2019).","journal-title":"Hum. Mutat."},{"key":"841_CR16","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.molcel.2013.10.004","volume":"52","author":"LC Young","year":"2013","unstructured":"Young, L. C. et al. An MRAS, SHOC2, and SCRIB complex coordinates ERK pathway activation with polarity and tumorigenic growth. Mol. Cell 52, 679\u2013692 (2013).","journal-title":"Mol. Cell"},{"key":"841_CR17","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.celrep.2019.08.090","volume":"29","author":"R Sulahian","year":"2019","unstructured":"Sulahian, R. et al. Synthetic lethal interaction of SHOC2 sepletion with MEK inhibition in RAS-driven cancers. Cell Rep. 29, 118\u2013134 (2019).","journal-title":"Cell Rep."},{"key":"841_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10367-x","volume":"10","author":"GG Jones","year":"2019","unstructured":"Jones, G. G. et al. SHOC2 phosphatase-dependent RAF dimerization mediates resistance to MEK inhibition in RAS-mutant cancers. Nat. Commun. 10, 2532 (2019).","journal-title":"Nat. Commun."},{"key":"841_CR19","doi-asserted-by":"publisher","first-page":"41797","DOI":"10.1074\/jbc.M112.390906","volume":"287","author":"FM Kaplan","year":"2012","unstructured":"Kaplan, F. M. et al. SHOC2 and CRAF mediate ERK1\/2 reactivation in mutant NRAS-mediated resistance to RAF inhibitor. J. Biol. Chem. 287, 41797\u201341807 (2012).","journal-title":"J. Biol. Chem."},{"key":"841_CR20","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1158\/1541-7786.MCR-20-0664","volume":"19","author":"H Terai","year":"2021","unstructured":"Terai, H. et al. SHOC2 is a critical modulator of sensitivity to EGFR-TKIs in non-small cell lung cancer cells. Mol. Cancer Res. 19, 317\u2013328 (2021).","journal-title":"Mol. Cancer Res."},{"key":"841_CR21","doi-asserted-by":"publisher","first-page":"13330","DOI":"10.1073\/pnas.1902658116","volume":"116","author":"I Boned Del Rio","year":"2019","unstructured":"Boned Del Rio, I. et al. SHOC2 complex-driven RAF dimerization selectively contributes to ERK pathway dynamics. Proc. Natl Acad. Sci. USA 116, 13330\u201313339 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"841_CR22","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41586-020-2099-x","volume":"580","author":"K Han","year":"2020","unstructured":"Han, K. et al. CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities. Nature 580, 136\u2013141 (2020).","journal-title":"Nature"},{"key":"841_CR23","doi-asserted-by":"publisher","first-page":"a033621","DOI":"10.1101\/cshperspect.a033621","volume":"8","author":"LC Young","year":"2018","unstructured":"Young, L. C. & Rodriguez-Viciana, P. MRAS: a close but understudied member of the RAS family. Cold Spring Harb. Perspect. Med. 8, a033621 (2018).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"841_CR24","doi-asserted-by":"publisher","first-page":"3536","DOI":"10.1073\/pnas.1805919116","volume":"116","author":"P Kota","year":"2019","unstructured":"Kota, P. et al. M-Ras\/Shoc2 signaling modulates E-cadherin turnover and cell-cell adhesion during collective cell migration. Proc. Natl Acad. Sci. USA 116, 3536\u20133545 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"841_CR25","doi-asserted-by":"publisher","first-page":"e91225","DOI":"10.1172\/jci.insight.91225","volume":"2","author":"EM Higgins","year":"2017","unstructured":"Higgins, E. M. et al. Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy. JCI Insight 2, e91225 (2017).","journal-title":"JCI Insight"},{"key":"841_CR26","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1002\/ajmg.a.61261","volume":"179","author":"H Suzuki","year":"2019","unstructured":"Suzuki, H. et al. Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers. Am. J. Med. Genet. A 179, 1628\u20131630 (2019).","journal-title":"Am. J. Med. Genet. A"},{"key":"841_CR27","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1042\/BST20160154","volume":"45","author":"I Verbinnen","year":"2017","unstructured":"Verbinnen, I., Ferreira, M. & Bollen, M. Biogenesis and activity regulation of protein phosphatase 1. Biochem. Soc. Trans. 45, 89\u201399 (2017).","journal-title":"Biochem. Soc. Trans."},{"key":"841_CR28","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.trsl.2014.07.001","volume":"164","author":"L Korrodi-Gregorio","year":"2014","unstructured":"Korrodi-Gregorio, L., Esteves, S. L. & Fardilha, M. Protein phosphatase 1 catalytic isoforms: specificity toward interacting proteins. Transl. Res. 164, 366\u2013391 (2014).","journal-title":"Transl. Res."},{"key":"841_CR29","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1111\/j.1742-4658.2012.08509.x","volume":"280","author":"W Peti","year":"2013","unstructured":"Peti, W., Nairn, A. C. & Page, R. Structural basis for protein phosphatase 1 regulation and specificity. FEBS J. 280, 596\u2013611 (2013).","journal-title":"FEBS J."},{"key":"841_CR30","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1002\/ajmg.a.38070","volume":"173","author":"D Bertola","year":"2017","unstructured":"Bertola, D. et al. The recurrent PPP1CB mutation p.Pro49Arg in an additional Noonan-like syndrome individual: broadening the clinical phenotype. Am. J. Med. Genet. A 173, 824\u2013828 (2017).","journal-title":"Am. J. Med. Genet. A"},{"key":"841_CR31","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1002\/ajmg.a.37781","volume":"170","author":"KW Gripp","year":"2016","unstructured":"Gripp, K. W. et al. A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair. Am. J. Med. Genet. A 170, 2237\u20132247 (2016).","journal-title":"Am. J. Med. Genet. A"},{"key":"841_CR32","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1002\/ajmg.a.62089","volume":"185","author":"V Huckstadt","year":"2021","unstructured":"Huckstadt, V., Chinton, J., Gomez, A., Obregon, M. G. & Gravina, L. P. Noonan syndrome with loose anagen hair with variants in the PPP1CB gene: First familial case reported. Am. J. Med. Genet A 185, 1256\u20131260 (2021).","journal-title":"Am. J. Med. Genet A"},{"key":"841_CR33","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/ajmg.a.38056","volume":"173","author":"RM Zambrano","year":"2017","unstructured":"Zambrano, R. M. et al. Further evidence that variants in PPP1CB cause a rasopathy similar to Noonan syndrome with loose anagen hair. Am. J. Med. Genet A 173, 565\u2013567 (2017).","journal-title":"Am. J. Med. Genet A"},{"key":"841_CR34","doi-asserted-by":"publisher","first-page":"106061","DOI":"10.1016\/j.pep.2022.106061","volume":"193","author":"K Snead","year":"2022","unstructured":"Snead, K., Wall, V., Ambrose, H., Esposito, D. & Drew, M. Polycistronic baculovirus expression of SUGT1 enables high-yield production of recombinant leucine-rich repeat proteins and protein complexes. Protein Expr. Purif. 193, 106061 (2022).","journal-title":"Protein Expr. Purif."},{"key":"841_CR35","doi-asserted-by":"publisher","first-page":"6903","DOI":"10.1073\/pnas.95.12.6903","volume":"95","author":"LM Selfors","year":"1998","unstructured":"Selfors, L. M., Schutzman, J. L., Borland, C. Z. & Stern, M. J. soc-2 encodes a leucine-rich repeat protein implicated in fibroblast growth factor receptor signaling. Proc. Natl Acad. Sci. USA 95, 6903\u20136908 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"841_CR36","doi-asserted-by":"publisher","first-page":"31267","DOI":"10.1074\/jbc.M505503200","volume":"280","author":"M Ye","year":"2005","unstructured":"Ye, M. et al. Crystal structure of M-Ras reveals a GTP-bound \u201coff\u201d state conformation of Ras family small GTPases. J. Biol. Chem. 280, 31267\u201331275 (2005).","journal-title":"J. Biol. Chem."},{"key":"841_CR37","doi-asserted-by":"publisher","first-page":"4097","DOI":"10.1073\/pnas.1317395111","volume":"111","author":"MS Choy","year":"2014","unstructured":"Choy, M. S. et al. Understanding the antagonism of retinoblastoma protein dephosphorylation by PNUTS provides insights into the PP1 regulatory code. Proc. Natl Acad. Sci. USA 111, 4097\u20134102 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"841_CR38","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1002\/cbic.202000669","volume":"22","author":"F Salvi","year":"2021","unstructured":"Salvi, F. et al. Towards dissecting the mechanism of protein phosphatase-1 inhibition by its C-terminal phosphorylation. ChemBioChem 22, 834\u2013838 (2021).","journal-title":"ChemBioChem"},{"key":"841_CR39","doi-asserted-by":"publisher","first-page":"18817","DOI":"10.1074\/jbc.M300175200","volume":"278","author":"P Wakula","year":"2003","unstructured":"Wakula, P., Beullens, M., Ceulemans, H., Stalmans, W. & Bollen, M. Degeneracy and function of the ubiquitous RVXF motif that mediates binding to protein phosphatase-1. J. Biol. Chem. 278, 18817\u201318823 (2003).","journal-title":"J. Biol. Chem."},{"key":"841_CR40","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.chembiol.2009.02.012","volume":"16","author":"A Hendrickx","year":"2009","unstructured":"Hendrickx, A. et al. Docking motif-guided mapping of the interactome of protein phosphatase-1. Chem. Biol. 16, 365\u2013371 (2009).","journal-title":"Chem. Biol."},{"key":"841_CR41","doi-asserted-by":"publisher","first-page":"115596","DOI":"10.18632\/oncotarget.23313","volume":"8","author":"KH Lee","year":"2017","unstructured":"Lee, K. H. et al. Stabilization of Sur8 via PKC\u03b1\/\u2206 degradation promotes transformation and migration of colorectal cancer cells. Oncotarget 8, 115596\u2013115608 (2017).","journal-title":"Oncotarget"},{"key":"841_CR42","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1038\/ng.3901","volume":"49","author":"TF Meehan","year":"2017","unstructured":"Meehan, T. F. et al. Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium. Nat. Genet. 49, 1231\u20131238 (2017).","journal-title":"Nat. Genet."},{"key":"841_CR43","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.bbamcr.2018.07.019","volume":"1866","author":"M Ferreira","year":"2019","unstructured":"Ferreira, M., Beullens, M., Bollen, M. & Van Eynde, A. Functions and therapeutic potential of protein phosphatase 1: insights from mouse genetics. Biochim. Biophys. Acta Mol. Cell. Res. 1866, 16\u201330 (2019).","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"841_CR44","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1158\/2159-8290.CD-14-0729","volume":"4","author":"CE Burd","year":"2014","unstructured":"Burd, C. E. et al. Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma. Cancer Discov. 4, 1418\u20131429 (2014).","journal-title":"Cancer Discov."},{"key":"841_CR45","doi-asserted-by":"publisher","first-page":"112342","DOI":"10.1016\/j.yexcr.2020.112342","volume":"397","author":"T Endo","year":"2020","unstructured":"Endo, T. M-Ras is muscle-Ras, moderate-Ras, mineral-Ras, migration-Ras, and many more-Ras. Exp. Cell. Res. 397, 112342 (2020).","journal-title":"Exp. Cell. Res."},{"key":"841_CR46","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/nature02582","volume":"429","author":"M Terrak","year":"2004","unstructured":"Terrak, M., Kerff, F., Langsetmo, K., Tao, T. & Dominguez, R. Structural basis of protein phosphatase 1 regulation. Nature 429, 780\u2013784 (2004).","journal-title":"Nature"},{"key":"841_CR47","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/376745a0","volume":"376","author":"J Goldberg","year":"1995","unstructured":"Goldberg, J. et al. Three-dimensional structure of the catalytic subunit of protein serine\/threonine phosphatase-1. Nature 376, 745\u2013753 (1995).","journal-title":"Nature"},{"key":"841_CR48","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1002\/pro.3771","volume":"29","author":"M Kurcinski","year":"2020","unstructured":"Kurcinski, M., Badaczewska-Dawid, A., Kolinski, M., Kolinski, A. & Kmiecik, S. Flexible docking of peptides to proteins using CABS-dock. Protein Sci. 29, 211\u2013222 (2020).","journal-title":"Protein Sci."},{"key":"841_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17334-x","volume":"11","author":"B Hoermann","year":"2020","unstructured":"Hoermann, B. et al. Dissecting the sequence determinants for dephosphorylation by the catalytic subunits of phosphatases PP1 and PP2A. Nat. Commun. 11, 3583 (2020).","journal-title":"Nat. Commun."},{"key":"841_CR50","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1002\/dvdy.22343","volume":"239","author":"J Yi","year":"2010","unstructured":"Yi, J. et al. Endothelial SUR-8 acts in an ERK-independent pathway during atrioventricular cushion development. Dev. Dyn. 239, 2005\u20132013 (2010).","journal-title":"Dev. Dyn."},{"key":"841_CR51","doi-asserted-by":"publisher","first-page":"7145","DOI":"10.1128\/MCB.00476-06","volume":"26","author":"N Nunez Rodriguez","year":"2006","unstructured":"Nunez Rodriguez, N. et al. Characterization of R-ras3\/m-ras null mice reveals a potential role in trophic factor signaling. Mol. Cell. Biol. 26, 7145\u20137154 (2006).","journal-title":"Mol. Cell. Biol."},{"key":"841_CR52","doi-asserted-by":"crossref","unstructured":"Lai, L. P. et al. Classical RAS proteins are not essential for paradoxical ERK activation induced by RAF inhibitors. Proc. Natl Acad. Sci. USA 119, e2113491119 (2022).","DOI":"10.1073\/pnas.2113491119"},{"key":"841_CR53","doi-asserted-by":"publisher","first-page":"eaau6044","DOI":"10.1126\/sciadv.aau6044","volume":"4","author":"GS Kumar","year":"2018","unstructured":"Kumar, G. S. et al. Identification of the substrate recruitment mechanism of the muscle glycogen protein phosphatase 1 holoenzyme. Sci. Adv. 4, eaau6044 (2018).","journal-title":"Sci. Adv."},{"key":"841_CR54","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/S0301-472X(02)00904-9","volume":"30","author":"A Ehrhardt","year":"2002","unstructured":"Ehrhardt, A., Ehrhardt, G. R., Guo, X. & Schrader, J. W. Ras and relatives\u2013job sharing and networking keep an old family together. Exp. Hematol. 30, 1089\u20131106 (2002).","journal-title":"Exp. Hematol."},{"key":"841_CR55","doi-asserted-by":"crossref","unstructured":"Fedoryshchak, R. O. et al. Molecular basis for substrate specificity of the Phactr1\/PP1 phosphatase holoenzyme. eLife 9, e61509 (2020).","DOI":"10.7554\/eLife.61509"},{"key":"841_CR56","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1016\/j.str.2012.08.003","volume":"20","author":"N O\u2019Connell","year":"2012","unstructured":"O\u2019Connell, N. et al. The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme. Structure 20, 1746\u20131756 (2012).","journal-title":"Structure"},{"key":"841_CR57","doi-asserted-by":"publisher","first-page":"20472","DOI":"10.1073\/pnas.1908718116","volume":"116","author":"MS Choy","year":"2019","unstructured":"Choy, M. S. et al. SDS22 selectively recognizes and traps metal-deficient inactive PP1. Proc. Natl Acad. Sci. USA 116, 20472\u201320481 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"841_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28084-3","volume":"13","author":"JA Martinez Fiesco","year":"2022","unstructured":"Martinez Fiesco, J. A., Durrant, D. E., Morrison, D. K. & Zhang, P. Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding. Nat. Commun. 13, 486 (2022).","journal-title":"Nat. Commun."},{"key":"841_CR59","doi-asserted-by":"crossref","unstructured":"Kwon, J. J. & Hahn, W. C. A leucine-rich repeat protein provides a SHOC2 the RAS circuit: a structure\u2013function perspective. Mol. Cell Biol. 41, e00627-20 (2021).","DOI":"10.1128\/MCB.00627-20"},{"key":"841_CR60","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/febs.15450","volume":"288","author":"H Jang","year":"2021","unstructured":"Jang, H., Stevens, P., Gao, T. & Galperin, E. The leucine-rich repeat signaling scaffolds Shoc2 and Erbin: cellular mechanism and role in disease. FEBS J. 288, 721\u2013739 (2021).","journal-title":"FEBS J."},{"key":"841_CR61","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S0092-8674(00)81227-1","volume":"94","author":"DS Sieburth","year":"1998","unstructured":"Sieburth, D. S., Sun, Q. & Han, M. SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in C. elegans. Cell 94, 119\u2013130 (1998).","journal-title":"Cell"},{"key":"841_CR62","doi-asserted-by":"crossref","unstructured":"Talsania, K. et al. Genome assembly and annotation of the Trichoplusia ni Tni-FNL insect cell line enabled by long-read technologies. Genes (Basel) 10, 79 (2019).","DOI":"10.3390\/genes10020079"},{"key":"841_CR63","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/978-1-4939-6887-9_5","volume":"1586","author":"T Taylor","year":"2017","unstructured":"Taylor, T., Denson, J. P. & Esposito, D. Optimizing expression and solubility of proteins in E. coli using modified media and induction parameters. Methods Mol. Biol. 1586, 65\u201382 (2017).","journal-title":"Methods Mol. Biol."},{"key":"841_CR64","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.1021\/acs.analchem.9b05126","volume":"92","author":"K Kopra","year":"2020","unstructured":"Kopra, K. et al. Homogeneous dual-parametric-coupled assay for simultaneous nucleotide exchange and KRAS\/RAF-RBd interaction monitoring. Anal. Chem. 92, 4971\u20134979 (2020).","journal-title":"Anal. Chem."},{"key":"841_CR65","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1107\/S2053230X14015507","volume":"70","author":"A D\u2019Arcy","year":"2014","unstructured":"D\u2019Arcy, A., Bergfors, T., Cowan-Jacob, S. W. & Marsh, M. Microseed matrix screening for optimization in protein crystallization: what have we learned? Acta Crystallogr. F. Struct. Biol. Commun. 70, 1117\u20131126 (2014).","journal-title":"Acta Crystallogr. F. Struct. Biol. Commun."},{"key":"841_CR66","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. XDS. Acta Crystallogr. D. Biol. Crystallogr. 66, 125\u2013132 (2010).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"841_CR67","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1107\/S0907444913000061","volume":"69","author":"PR Evans","year":"2013","unstructured":"Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D. Biol. Crystallogr. 69, 1204\u20131214 (2013).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"841_CR68","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1107\/S0907444910045749","volume":"67","author":"MD Winn","year":"2011","unstructured":"Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D. Biol. Crystallogr. 67, 235\u2013242 (2011).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"841_CR69","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1107\/S2059798319011471","volume":"75","author":"D Liebschner","year":"2019","unstructured":"Liebschner, D. et al. Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D. Struct. Biol. 75, 861\u2013877 (2019).","journal-title":"Acta Crystallogr. D. Struct. Biol."},{"key":"841_CR70","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D. Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"841_CR71","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1107\/S0907444911001314","volume":"67","author":"GN Murshudov","year":"2011","unstructured":"Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D. Biol. Crystallogr. 67, 355\u2013367 (2011).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"841_CR72","first-page":"8","volume":"1","author":"LLC Schrodinger","year":"2015","unstructured":"Schrodinger, L. L. C. The PyMOL Molecular Graphics System version 1.8 (2015).","journal-title":"ersion"},{"key":"841_CR73","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/pro.3280","volume":"27","author":"E Jurrus","year":"2018","unstructured":"Jurrus, E. et al. Improvements to the APBS biomolecular solvation software suite. Protein Sci. 27, 112\u2013128 (2018).","journal-title":"Protein Sci."},{"key":"841_CR74","doi-asserted-by":"publisher","first-page":"e01456","DOI":"10.7554\/eLife.01456","volume":"2","author":"A Morin","year":"2013","unstructured":"Morin, A. et al. Collaboration gets the most out of software. eLife 2, e01456 (2013).","journal-title":"eLife"},{"key":"841_CR75","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1021\/acsomega.9b03639","volume":"5","author":"FA Siddiqui","year":"2020","unstructured":"Siddiqui, F. A. et al. PDE6D inhibitors with a new design principle selectively block K-Ras activity. ACS Omega 5, 832\u2013842 (2020).","journal-title":"ACS Omega"},{"key":"841_CR76","doi-asserted-by":"crossref","unstructured":"Kumar, G. S. et al. The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism. eLife 5, e16539 (2016).","DOI":"10.7554\/eLife.16539"},{"key":"841_CR77","doi-asserted-by":"publisher","first-page":"10054","DOI":"10.1002\/anie.201204308","volume":"51","author":"J Chatterjee","year":"2012","unstructured":"Chatterjee, J. et al. Development of a peptide that selectively activates protein phosphatase-1 in living cells. Angew. Chem. Int. Ed. Engl. 51, 10054\u201310059 (2012).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"841_CR78","doi-asserted-by":"publisher","first-page":"4646","DOI":"10.1111\/febs.14699","volume":"285","author":"J Yu","year":"2018","unstructured":"Yu, J., Deng, T. & Xiang, S. Structural basis for protein phosphatase 1 recruitment by glycogen-targeting subunits. FEBS J. 285, 4646\u20134659 (2018).","journal-title":"FEBS J."},{"key":"841_CR79","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1038\/nsmb.1868","volume":"17","author":"A Hirschi","year":"2010","unstructured":"Hirschi, A. et al. An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein. Nat. Struct. Mol. Biol. 17, 1051\u20131057 (2010).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"841_CR80","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1016\/j.celrep.2015.05.043","volume":"11","author":"MS Choy","year":"2015","unstructured":"Choy, M. S. et al. Structural and functional analysis of the GADD34:PP1 eIF2\u03b1 phosphatase. Cell Rep. 11, 1885\u20131891 (2015).","journal-title":"Cell Rep."},{"key":"841_CR81","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/nsmb.1786","volume":"17","author":"MJ Ragusa","year":"2010","unstructured":"Ragusa, M. J. et al. Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites. Nat. Struct. Mol. Biol. 17, 459\u2013464 (2010).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"841_CR82","doi-asserted-by":"publisher","first-page":"28874","DOI":"10.1074\/jbc.M703472200","volume":"282","author":"TD Hurley","year":"2007","unstructured":"Hurley, T. D. et al. Structural basis for regulation of protein phosphatase 1 by inhibitor-2. J. Biol. Chem. 282, 28874\u201328883 (2007).","journal-title":"J. Biol. Chem."}],"container-title":["Nature Structural & Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00841-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00841-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00841-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T22:33:41Z","timestamp":1701124421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41594-022-00841-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,29]]},"references-count":82,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["841"],"URL":"https:\/\/doi.org\/10.1038\/s41594-022-00841-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.05.10.491335","asserted-by":"object"}]},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,29]]},"assertion":[{"value":"17 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"F.M. is a consultant for Amgen, Daiichi, Frontiers Med, Exuma Biotech, Ideaya Biosciences, Kura Oncology, Leidos Biomedical Research, PellePharm, Pfizer, P.M.V. Pharma, and Quanta Therapeutics. F.M. is a consultant and co-founder for (with ownership interest including stock options) BridgeBio, Olema Pharmaceuticals, and Quartz. F.M. has received research grants from Daiichi Sankyo and Gilead Sciences and has a current grant from Boehringer-Ingelheim. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}