{"doi":"10.1242/dev.02168","title":"MAP kinase subcellular localization controls both pattern and proliferation in the developing\n                    <i>Drosophila</i>\n                    wing","abstract":"<jats:p>Mitogen-activated protein kinases (MAPKs) phosphorylate target proteins in both the cytoplasm and nucleus, and a strong correlation exists between the subcellular localization of MAPK and resulting cellular responses. It was thought that MAPK phosphorylation was always followed by rapid nuclear translocation. However, we and others have found that MAPK phosphorylation is not always sufficient for nuclear translocation in vivo. In the developing Drosophila wing, MAPK-mediated signaling is required both for patterning and for cell proliferation, although the mechanism of this differential control is not fully understood. Here, we show that phosphorylated MAPK (pMAPK) is held in the cytoplasm in differentiating larval and pupal wing vein cells, and we show that this cytoplasmic hold is required for vein cell fate. At the same time, we show that MAPK does move into the nucleus of other wing cells where it promotes cell proliferation. We propose a novel Ras pathway bifurcation in Drosophila and our results suggest a mechanism by which MAPK phosphorylation can signal two different cellular outcomes (differentiation versus proliferation) based on the subcellular localization of MAPK.</jats:p>","journal":"Development","year":2006,"id":684656,"datarank":0.5742962094733643,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.0,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"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":1788656,"name":"Alysia D. Vrailas","orcid":null,"position":1,"is_corresponding":false},{"id":1788658,"name":"Aloma B. Rodrigues","orcid":null,"position":2,"is_corresponding":false},{"id":1788659,"name":"Summer Cook","orcid":null,"position":3,"is_corresponding":false},{"id":1788660,"name":"Maureen A. Powers","orcid":null,"position":4,"is_corresponding":false},{"id":1788661,"name":"James A. Lorenzen","orcid":null,"position":5,"is_corresponding":false},{"id":1788662,"name":"Lizabeth A. Perkins","orcid":null,"position":6,"is_corresponding":false},{"id":1761160,"name":"Kevin Moses","orcid":null,"position":7,"is_corresponding":false},{"id":965072,"name":"Daniel R. Marenda","orcid":"0000-0001-5388-8793","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"MAP kinase subcellular localization controls both pattern and proliferation in the developing\n                    <i>Drosophila</i>\n                    wing","abstract":"<jats:p>Mitogen-activated protein kinases (MAPKs) phosphorylate target proteins in both the cytoplasm and nucleus, and a strong correlation exists between the subcellular localization of MAPK and resulting cellular responses. It was thought that MAPK phosphorylation was always followed by rapid nuclear translocation. However, we and others have found that MAPK phosphorylation is not always sufficient for nuclear translocation in vivo. In the developing Drosophila wing, MAPK-mediated signaling is required both for patterning and for cell proliferation, although the mechanism of this differential control is not fully understood. Here, we show that phosphorylated MAPK (pMAPK) is held in the cytoplasm in differentiating larval and pupal wing vein cells, and we show that this cytoplasmic hold is required for vein cell fate. At the same time, we show that MAPK does move into the nucleus of other wing cells where it promotes cell proliferation. We propose a novel Ras pathway bifurcation in Drosophila and our results suggest a mechanism by which MAPK phosphorylation can signal two different cellular outcomes (differentiation versus proliferation) based on the subcellular localization of MAPK.</jats:p>","is_dataset_classified":null,"base_score":3.828641396489095,"endowment":3.828641396489095,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16308331","pmcid":"PMC2032010","openalex_id":"https://openalex.org/W2091587849","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM61707","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM061707","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"P01 HD39942","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"F32 GM073608","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY012537","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY12537","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008490","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"1 F32 GM073608","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"P01 HD039942","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01EY012537-06","title":"Retina: Map kinase regulates cell fate"},{"funder_name":"National Institutes of Health","grant_id":"1F32GM073608-01A1","title":"Cancer: MAPK phosphorylation and nuclear translocation"}],"total_grants":11,"fwci":1.6403,"citation_percentile":0.81407867,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2032010","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2032010","host_type":"repository"},{"url":"http://journals.biologists.com/dev/article-pdf/133/1/43/1153412/43.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/dev.02168","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16308331","host_type":"repository"},{"url":"http://dev.biologists.org/content/133/1/43.full.pdf","host_type":""},{"url":"https://dx.doi.org/10.1242/dev.02168","host_type":""}],"fields_of_study":["Cellular Mechanics and Interactions","Hippo pathway signaling and YAP/TAZ","Developmental Biology and Gene Regulation","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Cell Differentiation","Cell Nucleus","Cytoplasm","Drosophila","Flow Cytometry","Hot Temperature","Immunohistochemistry","Phosphorylation","Wings, Animal","Signal Transduction","HSP70 Heat-Shock Proteins","Mitogen-Activated Protein Kinases","Protein Transport","Cell Proliferation"],"keywords":["Biology","Cell biology","MAPK/ERK pathway","Cytoplasm","Phosphorylation","Kinase","Subcellular localization","Nucleus","Nuclear localization sequence","Cell growth","Mitogen-activated protein kinase","Protein kinase A","Signal transduction","Genetics","Cell Nucleus","Hot Temperature","Cell Differentiation","Flow Cytometry","Immunohistochemistry","Protein Transport","Animals","Wings, Animal","Drosophila","HSP70 Heat-Shock Proteins","Mitogen-Activated Protein Kinases","Cell Proliferation"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T14:40:26.831928Z","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":[]}