{"doi":"10.1371/journal.pone.0109530","title":"Drosophila Tribbles Antagonizes Insulin Signaling-Mediated Growth and Metabolism via Interactions with Akt Kinase","abstract":null,"journal":"PLoS ONE","year":2014,"id":668851,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"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":1746733,"name":"Zachary Sebo","orcid":null,"position":1,"is_corresponding":false},{"id":365603,"name":"Laramie Pence","orcid":null,"position":2,"is_corresponding":false},{"id":703604,"name":"Leonard L. Dobens","orcid":"0000-0003-1239-066X","position":3,"is_corresponding":false},{"id":250822,"name":"Rahul Das","orcid":"0000-0001-9445-8562","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Drosophila Tribbles Antagonizes Insulin Signaling-Mediated Growth and Metabolism via Interactions with Akt Kinase","abstract":"Drosophila Tribbles (Trbl) is the founding member of the Trib family of kinase-like docking proteins that modulate cell signaling during proliferation, migration and growth. In a wing misexpression screen for Trbl interacting proteins, we identified the Ser/Thr protein kinase Akt1. Given the central role of Akt1 in insulin signaling, we tested the function of Trbl in larval fat body, a tissue where rapid increases in size are exquisitely sensitive to insulin/insulin-like growth factor levels. Consistent with a role in antagonizing insulin-mediated growth, trbl RNAi knockdown in the fat body increased cell size, advanced the timing of pupation and increased levels of circulating triglyceride. Complementarily, overexpression of Trbl reduced fat body cell size, decreased overall larval size, delayed maturation and lowered levels of triglycerides, while circulating glucose levels increased. The conserved Trbl kinase domain is required for function in vivo and for interaction with Akt in a yeast two-hybrid assay. Consistent with direct regulation of Akt, overexpression of Trbl in the fat body decreased levels of activated Akt (pSer505-Akt) while misexpression of trbl RNAi increased phospho-Akt levels, and neither treatment affected total Akt levels. Trbl misexpression effectively suppressed Akt-mediated wing and muscle cell size increases and reduced phosphorylation of the Akt target FoxO (pSer256-FoxO). Taken together, these data show that Drosophila Trbl has a conserved role to bind Akt and block Akt-mediated insulin signaling, and implicate Trib proteins as novel sites of signaling pathway integration that link nutrient availability with cell growth and proliferation.","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":"25329475","pmcid":"PMC4198113","openalex_id":null,"authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM084947","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM084947-08","title":"Drosophila Transgenic RNAi Resource Project"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0109530&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0109530","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4198113","host_type":"repository"},{"url":"https://doaj.org/article/253091a6eefa4f41823f81e8aabce497","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4198113","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4198113?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1371/journal.pone.0109530","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/25329475","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pone.0109530","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0109530","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Drosophila melanogaster","Insulin","Cell Cycle Proteins","Drosophila Proteins","Signal Transduction","Cell Cycle","Cell Proliferation","RNA Interference","Protein Binding","Phosphorylation","Proto-Oncogene Proteins c-akt","Protein Serine-Threonine Kinases"],"keywords":["Science","Q","Cell Cycle","R","Cell Cycle Proteins","Protein Serine-Threonine Kinases","Drosophila melanogaster","Medicine","Animals","Drosophila Proteins","Insulin","RNA Interference","Phosphorylation","Proto-Oncogene Proteins c-akt","Research Article","Cell Proliferation","Protein Binding","Signal Transduction"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-14T12:58:54.540122Z","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":[]}