{"id":"https://openalex.org/W601398342","doi":"https://doi.org/10.4049/jimmunol.182.supp.49.8","title":"Increased ERK1/2 activation leads to sustained T cell receptor signaling in rheumatoid arthritis (49.8)","display_name":"Increased ERK1/2 activation leads to sustained T cell receptor signaling in rheumatoid arthritis (49.8)","publication_year":2009,"publication_date":"2009-04-01","ids":{"openalex":"https://openalex.org/W601398342","doi":"https://doi.org/10.4049/jimmunol.182.supp.49.8","mag":"601398342"},"language":"en","primary_location":{"id":"doi:10.4049/jimmunol.182.supp.49.8","doi":"https://doi.org/10.4049/jimmunol.182.supp.49.8","is_oa":false,"landing_page_url":"https://doi.org/10.4049/jimmunol.182.supp.49.8","pdf_url":null,"source":{"id":"https://openalex.org/S38008053","display_name":"The Journal of Immunology","issn_l":"0022-1767","issn":["0022-1767","1550-6606"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4320800377","host_organization_name":"American Association of Immunologists","host_organization_lineage":["https://openalex.org/P4320800377"],"host_organization_lineage_names":["American Association of Immunologists"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Immunology","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5062811978","display_name":"Karnail Singh","orcid":"https://orcid.org/0000-0002-7503-1747","observed_orcids":["https://orcid.org/0000-0002-7503-1747"]},"institutions":[{"id":"https://openalex.org/I150468666","display_name":"Emory University","ror":"https://ror.org/03czfpz43","country_code":"US","type":"education","lineage":["https://openalex.org/I150468666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Karnail Singh","raw_affiliation_strings":["Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]},{"raw_affiliation_string":"1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071223265","display_name":"Pratima Deshpande","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I150468666","display_name":"Emory University","ror":"https://ror.org/03czfpz43","country_code":"US","type":"education","lineage":["https://openalex.org/I150468666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Pratima Deshpande","raw_affiliation_strings":["Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]},{"raw_affiliation_string":"1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009827644","display_name":"Sergey Pryshchep","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I150468666","display_name":"Emory University","ror":"https://ror.org/03czfpz43","country_code":"US","type":"education","lineage":["https://openalex.org/I150468666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sergey Pryshchep","raw_affiliation_strings":["Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]},{"raw_affiliation_string":"1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056587089","display_name":"Cornelia M. Weyand","orcid":"https://orcid.org/0000-0003-2230-9802","observed_orcids":["https://orcid.org/0000-0003-2230-9802"]},"institutions":[{"id":"https://openalex.org/I150468666","display_name":"Emory University","ror":"https://ror.org/03czfpz43","country_code":"US","type":"education","lineage":["https://openalex.org/I150468666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Cornelia M Weyand","raw_affiliation_strings":["Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]},{"raw_affiliation_string":"1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5016250824","display_name":"J\u00f6rg J. Goronzy","orcid":"https://orcid.org/0000-0001-7670-1856","observed_orcids":["https://orcid.org/0000-0001-7670-1856"]},"institutions":[{"id":"https://openalex.org/I150468666","display_name":"Emory University","ror":"https://ror.org/03czfpz43","country_code":"US","type":"education","lineage":["https://openalex.org/I150468666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jorg J Goronzy","raw_affiliation_strings":["Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University , Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]},{"raw_affiliation_string":"1Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University, Atlanta, GA","institution_ids":["https://openalex.org/I150468666"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I150468666"],"apc_list":{"value":3500,"currency":"USD","value_usd":3500},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"182","issue":"Supplement_1","first_page":"49.8","last_page":"49.8"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10200","display_name":"Rheumatoid Arthritis Research and Therapies","score":0.913100004196167,"subfield":{"id":"https://openalex.org/subfields/2745","display_name":"Rheumatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10200","display_name":"Rheumatoid Arthritis Research and Therapies","score":0.913100004196167,"subfield":{"id":"https://openalex.org/subfields/2745","display_name":"Rheumatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.07729999721050262,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13026","display_name":"Natural Compounds in Disease Treatment","score":0.002899999963119626,"subfield":{"id":"https://openalex.org/subfields/2707","display_name":"Complementary and alternative medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/rheumatoid-arthritis","display_name":"rheumatoid arthritis","score":0.9940000176429749},{"id":"https://openalex.org/keywords/erk1-2-activation","display_name":"ERK1/2 activation","score":0.843999981880188},{"id":"https://openalex.org/keywords/t-cell-receptor-signaling","display_name":"T cell receptor signaling","score":0.9950000047683716},{"id":"https://openalex.org/keywords/t-cell-activation-threshold","display_name":"T cell activation threshold","score":0.7910000085830688},{"id":"https://openalex.org/keywords/immunological-synapse","display_name":"immunological synapse","score":0.7160000205039978},{"id":"https://openalex.org/keywords/shp-1","display_name":"SHP-1","score":0.8759999871253967},{"id":"https://openalex.org/keywords/mek1-inhibition","display_name":"MEK1 inhibition","score":0.8159999847412109},{"id":"https://openalex.org/keywords/autoimmunity","display_name":"autoimmunity","score":0.7900000214576721},{"id":"https://openalex.org/keywords/immune-tolerance","display_name":"immune tolerance","score":0.6869999766349792},{"id":"https://openalex.org/keywords/zap-70","display_name":"ZAP-70","score":0.753000020980835},{"id":"https://openalex.org/keywords/nf-kappab","display_name":"NF-\u03baB","score":0.847000002861023},{"id":"https://openalex.org/keywords/cd4-and-cd8-t-cells","display_name":"CD4 and CD8 T cells","score":0.8550000190734863}],"concepts":[{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.6086481213569641},{"id":"https://openalex.org/C2776989580","wikidata":"https://www.wikidata.org/wiki/Q421320","display_name":"Ionomycin","level":3,"score":0.5905047655105591},{"id":"https://openalex.org/C24998067","wikidata":"https://www.wikidata.org/wiki/Q4114622","display_name":"Stimulation","level":2,"score":0.5502526760101318},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.5399084687232971},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.5280107855796814},{"id":"https://openalex.org/C148125776","wikidata":"https://www.wikidata.org/wiki/Q1622348","display_name":"CD28","level":4,"score":0.510426938533783},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.5031985640525818},{"id":"https://openalex.org/C19317047","wikidata":"https://www.wikidata.org/wiki/Q412037","display_name":"T-cell receptor","level":4,"score":0.4996178150177002},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.47104597091674805},{"id":"https://openalex.org/C2780405999","wikidata":"https://www.wikidata.org/wiki/Q3483597","display_name":"Co-stimulation","level":5,"score":0.47005048394203186},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4492083489894867},{"id":"https://openalex.org/C2777575956","wikidata":"https://www.wikidata.org/wiki/Q187255","display_name":"Rheumatoid arthritis","level":2,"score":0.43736159801483154},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.4359831213951111},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3851219415664673},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.37709879875183105},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.37302854657173157},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3562132716178894}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.4049/jimmunol.182.supp.49.8","doi":"https://doi.org/10.4049/jimmunol.182.supp.49.8","is_oa":false,"landing_page_url":"https://doi.org/10.4049/jimmunol.182.supp.49.8","pdf_url":null,"source":{"id":"https://openalex.org/S38008053","display_name":"The Journal of Immunology","issn_l":"0022-1767","issn":["0022-1767","1550-6606"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4320800377","host_organization_name":"American Association of Immunologists","host_organization_lineage":["https://openalex.org/P4320800377"],"host_organization_lineage_names":["American Association of Immunologists"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Immunology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9476000070571899,"display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","score":0.7799999713897705,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2389794721","https://openalex.org/W2009016562","https://openalex.org/W4245295665","https://openalex.org/W2148517786","https://openalex.org/W3193529407","https://openalex.org/W2926473910","https://openalex.org/W1971240700","https://openalex.org/W2024281858","https://openalex.org/W2162856391","https://openalex.org/W2016819838"],"abstract_inverted_index":{"Abstract":[0],"Immune":[1],"responses":[2],"to":[3,82,85,122,131,136,149,193],"citrullinated":[4],"neoantigens":[5],"indicate":[6],"a":[7,97,157],"tolerance":[8,195],"defect":[9,98],"in":[10,22,68,160,200],"rheumatoid":[11],"arthritis":[12],"(RA).":[13],"We":[14,184],"examined":[15],"the":[16,27,137,146,161,178],"hypothesis":[17],"that":[18,186],"abnormal":[19],"TCR":[20,102,147,191],"signaling":[21,50],"RA":[23,35,79,141,166],"T":[24,30,76,142],"cells":[25,31,77,143],"lowers":[26],"activation":[28],"threshold.":[29],"from":[32,78],"33":[33,38],"seropositive":[34],"patients":[36,80],"and":[37,57,71,74,107,116,124,144,167,197],"controls":[39,83],"were":[40],"stimulated":[41],"by":[42,53,203],"CD3/CD28":[43],"crosslinking":[44],"or":[45],"superantigen-coated":[46],"dendritic":[47],"cells.":[48],"Activation-induced":[49],"was":[51,66,90,109,119,155],"quantified":[52],"PhosFlow,":[54],"Western":[55],"blotting,":[56],"confocal":[58],"microscopy.":[59],"Basal":[60],"as":[61,63],"well":[62],"post-stimulation":[64],"p-ERK":[65],"higher":[67],"nai\u0308ve,":[69],"memory":[70],"effector":[72],"CD4":[73],"CD8":[75],"compared":[81],"(p<0.01":[84],"p<0.001).":[86],"Increased":[87,127,152],"ERK":[88,125,128,153,188],"phosphorylation":[89],"also":[91,156],"observed":[92],"upon":[93],"PMA/ionomycin":[94],"stimulation":[95],"suggesting":[96],"distal":[99],"of":[100,105,134,140,165,180],"early":[101],"signals.":[103],"Phosphorylation":[104],"ZAP70":[106],"NFk-B":[108],"only":[110],"elevated":[111],"at":[112],"late":[113],"time":[114],"points,":[115],"this":[117],"increase":[118],"completely":[120],"amenable":[121],"MEK1":[123],"inhibitors.":[126],"responsiveness":[129,154],"led":[130],"delayed":[132,177],"recruitment":[133],"SHP-1":[135],"immunological":[138],"synapse":[139],"lowered":[145],"threshold":[148],"suboptimal":[150],"stimulation.":[151],"characteristic":[158],"finding":[159],"SKG":[162],"mouse":[163],"model":[164],"preceded":[168],"clinical":[169],"symptoms.":[170],"MEK-1":[171],"inhibition":[172],"with":[173],"subtherapeutic":[174],"doses":[175],"significantly":[176],"onset":[179],"less":[181],"severe":[182],"disease.":[183],"propose":[185],"increased":[187],"activity":[189],"tunes":[190],"thresholds":[192],"impair":[194],"mechanism":[196],"induce":[198],"autoimmunity":[199],"RA.":[201],"Supported":[202],"RO1-AR41974":[204],"&":[205],"AI":[206],"44142.":[207]},"counts_by_year":[],"updated_date":"2026-08-21T09:56:20.448147","created_date":"2025-10-10T00:00:00"}
