{"doi":"10.1074/jbc.m116.767087","title":"The WW domain of the scaffolding protein IQGAP1 is neither necessary nor sufficient for binding to the MAPKs ERK1 and ERK2","abstract":null,"journal":"Journal of Biological Chemistry","year":2017,"id":621318,"datarank":0.4943755299006494,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.0,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"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":1344284,"name":"Leonila Lagunes","orcid":"0000-0001-9436-1525","position":1,"is_corresponding":false},{"id":1604240,"name":"Ronak Zebarjedi","orcid":null,"position":2,"is_corresponding":false},{"id":997227,"name":"Lee Bardwell","orcid":"0000-0002-2393-8363","position":3,"is_corresponding":false},{"id":997780,"name":"A. Jane Bardwell","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The WW domain of the scaffolding protein IQGAP1 is neither necessary nor sufficient for binding to the MAPKs ERK1 and ERK2","abstract":"Mitogen-activated protein kinase (MAPK) scaffold proteins, such as IQ motif containing GTPase activating protein 1 (IQGAP1), are promising targets for novel therapies against cancer and other diseases. Such approaches require accurate information about which domains on the scaffold protein bind to the kinases in the MAPK cascade. Results from previous studies have suggested that the WW domain of IQGAP1 binds to the cancer-associated MAPKs ERK1 and ERK2, and that this domain might thus offer a new tool to selectively inhibit MAPK activation in cancer cells. The goal of this work was therefore to critically evaluate which IQGAP1 domains bind to ERK1/2. Here, using quantitative in vitro binding assays, we show that the IQ domain of IQGAP1 is both necessary and sufficient for binding to ERK1 and ERK2, as well as to the MAPK kinases MEK1 and MEK2. Furthermore, we show that the WW domain is not required for ERK-IQGAP1 binding, and contributes little or no binding energy to this interaction, challenging previous models of how WW-based peptides might inhibit tumorigenesis. Finally, we show that the ERK2-IQGAP1 interaction does not require ERK2 phosphorylation or catalytic activity and does not involve known docking recruitment sites on ERK2, and we obtain an estimate of the dissociation constant ( K d ) for this interaction of 8 μm. These results prompt a re-evaluation of published findings and a refined model of IQGAP scaffolding.","is_dataset_classified":null,"base_score":3.295836866004329,"endowment":3.295836866004329,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28396345","pmcid":"PMC5448102","openalex_id":"https://openalex.org/W2607204117","authors":[],"funders":[{"funder_name":"National Institute of General Medical Sciences","grant_id":"P50 GM76516","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA062203","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"P50 GM076516","title":null},{"funder_name":"National Institutes of Health","grant_id":"4P50GM076516-10","title":"Systems Biology of Morphogeneisis and Spatial Information Flow"}],"total_grants":4,"fwci":1.0139,"citation_percentile":0.74458803,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":6}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820427620/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820427620/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820427620?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820427620?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M116.767087","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m116.767087","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28396345","host_type":"repository"},{"url":"https://escholarship.org/uc/item/7bt750s1","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5448102","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5448102","host_type":"repository"},{"url":"http://www.jbc.org/content/292/21/8750.full.pdf","host_type":""},{"url":"https://dx.doi.org/10.1074/jbc.m116.767087","host_type":""},{"url":"https://escholarship.org/content/qt7bt750s1/qt7bt750s1.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1074/jbc.m116.767087","host_type":""}],"fields_of_study":["Signaling Pathways in Disease","Ubiquitin and proteasome pathways","14-3-3 protein interactions","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Protein Domains","Humans","Protein Binding","Mitogen-Activated Protein Kinase 1","ras GTPase-Activating Proteins","Mitogen-Activated Protein Kinase 3","MAP Kinase Kinase 1","MAP Kinase Kinase 2"],"keywords":["Scaffold protein","IQGAP1","Scaffold","Domain (mathematical analysis)","Cell biology","Chemistry","Business","Computer science","Biology","Mathematics","Signal transduction","Protein kinase","Cancer","Protein-protein interaction","Mitogen-activated protein kinase (MAPK)","Cell signaling","Protein Complex","Extracellular-signal-regulated Kinase (Erk)","570","Biochemistry & Molecular Biology","Biomedical and clinical sciences","mitogen-activated protein kinase","MAP Kinase Kinase 2","MAP Kinase Kinase 1","610","Medical and Health Sciences","Protein Domains","Humans","Minority Health","Mitogen-Activated Protein Kinase 1","Mitogen-Activated Protein Kinase 3","Biological Sciences","Health Disparities","Chemical sciences","ras GTPase-Activating Proteins","Biochemistry and Cell Biology","Generic health relevance","extracellular-signal-regulated kinase","Protein Binding"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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