{"doi":"10.1126/science.7839144","title":"Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms","abstract":"<jats:p>Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.</jats:p>","journal":"Science","year":1995,"id":24863,"datarank":17.363145249055915,"base_score":7.354362330421477,"endowment":7.354362330421477,"self_citation_contribution":1.1031543495632217,"citation_network_contribution":16.259990899492692,"self_endowment_contribution":1.1031543495632217,"citer_contribution":16.259990899492692,"corpus_percentile":null,"corpus_rank":null,"citation_count":1562,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":147943,"name":"Joël Raingeaud","orcid":null,"position":1,"is_corresponding":false},{"id":147944,"name":"Tamera Barrett","orcid":null,"position":2,"is_corresponding":false},{"id":147945,"name":"I-Huan Wu","orcid":null,"position":3,"is_corresponding":false},{"id":123575,"name":"Jiahuai Han","orcid":null,"position":4,"is_corresponding":false},{"id":147946,"name":"Richard J. Ulevitch","orcid":null,"position":5,"is_corresponding":false},{"id":119957,"name":"Roger J. Davis","orcid":null,"position":6,"is_corresponding":false},{"id":147942,"name":"Benoit Dérijard","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":7.354362330421477,"endowment":7.354362330421477,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"7839144","pmcid":null,"openalex_id":"https://openalex.org/W1998487776","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM37696","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI15136","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA58396","title":null}],"total_grants":3,"fwci":58.3909,"citation_percentile":0.99967443,"influential_citations":100,"citation_trend":[{"year":2012,"count":27},{"year":2013,"count":24},{"year":2014,"count":27},{"year":2015,"count":14},{"year":2016,"count":24},{"year":2017,"count":19},{"year":2018,"count":16},{"year":2019,"count":18},{"year":2020,"count":14},{"year":2021,"count":19},{"year":2022,"count":17},{"year":2023,"count":11},{"year":2024,"count":8},{"year":2025,"count":11},{"year":2026,"count":4}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.7839144","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.7839144","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/7839144","host_type":"repository"}],"fields_of_study":["Melanoma and MAPK Pathways","Cancer Mechanisms and Therapy","Protein Kinase Regulation and GTPase Signaling","Biology","Medicine","Amino Acid Sequence","Animals","Base Sequence","Calcium-Calmodulin-Dependent Protein Kinases","Cell Line","Cloning, Molecular","Enzyme Activation","Humans","JNK Mitogen-Activated Protein Kinases","MAP Kinase Kinase 3","MAP Kinase Kinase 4","Mitogen-Activated Protein Kinase 1","Mitogen-Activated Protein Kinase Kinases","Mitogen-Activated Protein Kinases","Molecular Sequence Data","Phosphorylation","Protein Serine-Threonine Kinases","Protein-Tyrosine Kinases","Signal Transduction","Substrate Specificity","Transfection","p38 Mitogen-Activated Protein Kinases"],"mesh_terms":["Amino Acid Sequence","Animals","Base Sequence","Cell Line","Cloning, Molecular","Enzyme Activation","Humans","Molecular Sequence Data","Phosphorylation","Protein-Tyrosine Kinases","Substrate Specificity","Transfection","Signal Transduction","Protein Serine-Threonine Kinases","Calcium-Calmodulin-Dependent Protein Kinases","Mitogen-Activated Protein Kinase 1","Mitogen-Activated Protein Kinases","Mitogen-Activated Protein Kinase Kinases","JNK Mitogen-Activated Protein Kinases","p38 Mitogen-Activated Protein Kinases","MAP Kinase Kinase 3","MAP Kinase Kinase 4"],"keywords":["MAP2K7","MAP kinase kinase kinase","Mitogen-activated protein kinase kinase","MAPK7","MAPKAPK2","MAPK14","ASK1","Mitogen-activated protein kinase","Cyclin-dependent kinase 9","c-Raf","p38 mitogen-activated protein kinases","Kinase","Cell biology","Cyclin-dependent kinase 2","Signal transduction","MAPK/ERK pathway","Biology","Chemistry","Protein kinase A"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T23:24:09.969420Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}