{"doi":"10.1002/ibd.21851","title":"Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1","abstract":null,"journal":"Inflammatory Bowel Diseases","year":2012,"id":607241,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":681973,"name":"Carmen Alonso","orcid":"0000-0002-7170-5724","position":1,"is_corresponding":false},{"id":1559177,"name":"Isabel Ballester","orcid":null,"position":2,"is_corresponding":false},{"id":1559178,"name":"Joo Hye Song","orcid":null,"position":3,"is_corresponding":false},{"id":1559179,"name":"Sun Young Chang","orcid":null,"position":4,"is_corresponding":false},{"id":1559180,"name":"Bayasi Guleng","orcid":null,"position":5,"is_corresponding":false},{"id":1559181,"name":"Seiji Arihiro","orcid":null,"position":6,"is_corresponding":false},{"id":321053,"name":"Peter J. Murray","orcid":"0000-0002-0742-1911","position":7,"is_corresponding":false},{"id":1559182,"name":"Ramnik Xavier","orcid":null,"position":8,"is_corresponding":false},{"id":882554,"name":"Koichi S. Kobayashi","orcid":"0000-0003-2930-0114","position":9,"is_corresponding":false},{"id":330851,"name":"Hans-Christian Reinecker","orcid":"0000-0001-8283-644X","position":10,"is_corresponding":false},{"id":442074,"name":"Yun Zhao","orcid":"0000-0003-4559-399X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1","abstract":"BACKGROUND: Genetic variants of nucleotide-binding oligomerization domain 2 (NOD2) lead to aberrant microbial recognition and can cause chronic inflammatory diseases in patients with Crohn's disease (CD). METHODS: We utilized gene-specific siRNA mediated knockdown and expression of guanine nucleotide exchange factor H1 (GEF-H1) in wildtype, Rip2-, and Nod2-deficient macrophages, HCT-116 and HEK 293 cells to determine the role of GEF-H1 in NOD2 and Rip2-mediated NF-κB-dependent induction of proinflammatory cytokine expression. Confocal microscopy was used to determine subcellular distribution of GEF-H1, Rip2, and NOD2. RESULTS: We identified GEF-H1 as an unexpected component of innate immune regulation during microbial pattern recognition by NOD2. Surprisingly, GEF-H1-mediated the activation of Rip2 during signaling by NOD2, but not in the presence of the 3020 insC variant of NOD2 associated with CD. GEF-H1 functioned downstream of NOD2 as part of Rip2-containing signaling complexes and was responsible for phosphorylation of Rip2 by Src tyrosine kinase. Rip2 variants lacking the tyrosine target of GEF-H1-mediated phosphorylation were unable to mediate NF-κB activation in Rip2-deficient macrophages and failed to transduce NOD2 signaling. GEF-H1 is required downstream of NOD2 as part of Rip2-containing signaling complexes for the activation of innate immune responses. CONCLUSIONS: GEF-H1 connects tyrosine kinase function to NOD-like receptor signaling and is fundamental to the regulation of microbial recognition by ubiquitous innate immune mechanisms mediated by Rip2 kinase.","is_dataset_classified":null,"base_score":3.784189633918261,"endowment":3.784189633918261,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21887730","pmcid":null,"openalex_id":"https://openalex.org/W2046874505","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK043351","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK033506","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK043351","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK068181","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R56 AI093588","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK074738","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P01 DK033506","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK068181","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK074738","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI113333","title":null}],"total_grants":10,"fwci":1.2555,"citation_percentile":0.78108736,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":5},{"year":2014,"count":3},{"year":2015,"count":3},{"year":2016,"count":3},{"year":2017,"count":6},{"year":2018,"count":3},{"year":2019,"count":3},{"year":2020,"count":3},{"year":2021,"count":3},{"year":2023,"count":2},{"year":2024,"count":4},{"year":2025,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/ibdjournal/article-pdf/18/4/603/23419361/ibd0603.pdf","host_type":"journal"},{"url":"https://academic.oup.com/ibdjournal/article-pdf/18/4/603/23419361/ibd0603.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1002/ibd.21851","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21887730","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3594873","host_type":"repository"}],"fields_of_study":["Immune Response and Inflammation","NF-κB Signaling Pathways","Inflammatory Bowel Disease","Cells, Cultured","Crohn Disease","Cytokines","Gene Knockdown Techniques","Guanine Nucleotide Exchange Factors","HCT116 Cells","HEK293 Cells","Humans","Immunity, Innate","Inflammation","Macrophages","NF-kappa B","Nod2 Signaling Adaptor Protein","Receptor-Interacting Protein Serine-Threonine Kinase 2","Rho Guanine Nucleotide Exchange Factors","src-Family Kinases"],"mesh_terms":["Cells, Cultured","Crohn Disease","Humans","Immunity, Innate","Inflammation","Macrophages","Cytokines","NF-kappa B","src-Family Kinases","Guanine Nucleotide Exchange Factors","HCT116 Cells","Nod2 Signaling Adaptor Protein","Receptor-Interacting Protein Serine-Threonine Kinase 2","Gene Knockdown Techniques","HEK293 Cells","Rho Guanine Nucleotide Exchange Factors"],"keywords":["NOD2","Innate immune system","Crohn's disease","Immune system","Immunology","Nucleotide","Disease","Medicine","NOD1","Inflammatory bowel disease","Biology","Genetics","Internal medicine","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T06:01:47.707563Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}