{"doi":"10.1074/jbc.ra119.007438","title":"The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases","abstract":null,"journal":"Journal of Biological Chemistry","year":2019,"id":642952,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"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":63441,"name":"Carol A. Fierke","orcid":"0000-0002-1481-0579","position":1,"is_corresponding":false},{"id":1672663,"name":"Desirée García-Torres","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases","abstract":"Ras family small GTPases undergo prenylation (such as farnesylation) for proper localization to the plasma membrane, where they can initiate oncogenic signaling pathways. Small GTP-binding protein GDP-dissociation stimulator (SmgGDS) proteins are chaperones that bind and traffic small GTPases, although their exact cellular function is unknown. Initially, SmgGDS proteins were classified as guanine nucleotide exchange factors, but recent findings suggest that SmgGDS proteins also regulate prenylation of small GTPases <i>in vivo</i> in a substrate-selective manner. SmgGDS-607 recognizes the polybasic region and the CAA<i>X</i> box of several small GTPases and inhibits prenylation by impeding their entry into the geranylgeranylation pathway. Here, using recombinant and purified enzymes for prenylation and protein-binding assays, we demonstrate that SmgGDS-607 differentially regulates farnesylation of several small GTPases. SmgGDS-607 inhibited farnesylation of some proteins, such as DiRas1, by sequestering the protein and limiting modification catalyzed by protein farnesyltransferase (FTase). We found that the competitive binding affinities of the small GTPase for SmgGDS-607 and FTase dictate the extent of this inhibition. Additionally, we discovered that SmgGDS-607 increases the rate of farnesylation of HRas by enhancing product release from FTase. Our work indicates that SmgGDS-607 binds to a broad range of small GTPases and does not require a PBR for recognition. Together, these results provide mechanistic insight into SmgGDS-607-mediated regulation of farnesylation of small GTPases and suggest that SmgGDS-607 has multiple modes of substrate recognition.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31197034","pmcid":"PMC6682747","openalex_id":"https://openalex.org/W31197034","authors":[],"funders":[{"funder_name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","grant_id":"5-R01-GM-040602","title":null},{"funder_name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","grant_id":"5T32GM008597","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM040602","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008597","title":null}],"total_grants":4,"fwci":0.0,"citation_percentile":0.00679916,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820302222/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820302222?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820302222?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.RA119.007438","host_type":"publisher"},{"url":"https://cyberleninka.ru/article/n/metodologicheskie-problemy-differentsiatsii-nauchnogo-i-psevdonauchnogo-tipov-obosnovaniya.pdf","host_type":"journal"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6682747","host_type":"repository"}],"fields_of_study":["Medical and Biological Sciences","Alkyl and Aryl Transferases","Amino Acid Motifs","Biocatalysis","GTP Phosphohydrolases","Guanine Nucleotide Exchange Factors","Humans","Kinetics","Monomeric GTP-Binding Proteins","Mutagenesis, Site-Directed","Protein Binding","Protein Prenylation","Proto-Oncogene Proteins p21(ras)","Recombinant Proteins","Substrate Specificity","Thermodynamics","Tumor Suppressor Proteins"],"mesh_terms":["Humans","GTP Phosphohydrolases","Monomeric GTP-Binding Proteins","Alkyl and Aryl Transferases","Guanine Nucleotide Exchange Factors","Tumor Suppressor Proteins","Recombinant Proteins","Mutagenesis, Site-Directed","Amino Acid Motifs","Protein Binding","Substrate Specificity","Kinetics","Thermodynamics","Proto-Oncogene Proteins p21(ras)","Protein Prenylation","Biocatalysis"],"keywords":["Pseudoscience","Epistemology","Set (abstract data type)","Mathematics","Computer science","Philosophy","Medicine","Alternative medicine","Cancer","Ras protein","Enzyme kinetics","Cell signaling","small GTPase","Protein Farnesylation","Protein Prenylation","Post-translational Modification (Ptm)","Gtpase Kras (Kras)","Small Gtp-binding Protein Gdp-dissociation Stimulator (Smggds)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T11:09:14.869540Z","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":[]}