{"corpus_id":41260472,"paper_sha":"3324c05e1e37cf640545b01cbefbb758f2eda750","doi":"10.1074/jbc.M707287200","arxiv_id":null,"pmid":17956870,"pmcid":null,"mag_id":2076763303,"dblp_id":null,"acl_id":null,"title":"Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms*","year":2007,"publication_date":"2007-12-14","venue":"Journal of Biological Chemistry","journal":{"name":"Journal of Biological Chemistry","pages":"36303 - 36313","volume":"282"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":39,"citation_count":80,"influential_citation_count":7,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Cell Line","mj":false,"ui":"D002460"},{"d":"Cell Proliferation","mj":true,"ui":"D049109"},{"d":"Epithelial Sodium Channels","mj":false,"qs":[{"q":"biosynthesis","mj":false,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D053503"},{"d":"Extracellular Signal-Regulated MAP Kinases","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D048049"},{"d":"Gene Expression","mj":false,"ui":"D015870"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Ion Transport","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D017136"},{"d":"Kidney Tubules, Collecting","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D007685"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Organ Specificity","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D009928"},{"d":"Phosphorylation","mj":false,"ui":"D010766"},{"d":"Protein Isoforms","mj":false,"qs":[{"q":"biosynthesis","mj":false,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D020033"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Sodium","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D012964"},{"d":"Transcription Factors","mj":false,"qs":[{"q":"biosynthesis","mj":true,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D014157"}],"chemicals":[{"n":"Dsip1 protein, mouse","ui":"C498608","reg":"0"},{"n":"Epithelial Sodium Channels","ui":"D053503","reg":"0"},{"n":"Protein Isoforms","ui":"D020033","reg":"0"},{"n":"TSC22D3 protein, human","ui":"C404226","reg":"0"},{"n":"Transcription Factors","ui":"D014157","reg":"0"},{"n":"Tsc22d3 protein, rat","ui":"C498609","reg":"0"},{"n":"Sodium","ui":"D012964","reg":"9NEZ333N27"},{"n":"Extracellular Signal-Regulated MAP Kinases","ui":"D048049","reg":"EC 2.7.11.24"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.jbc.org/article/S0021925818460826/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/3324c05e1e37cf640545b01cbefbb758f2eda750","s2_open_access_license":"CCBY","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Glucocorticoid-induced leucine zipper protein (GILZ) is expressed in both epithelial and immune tissues and modulates a variety of cellular functions, including proliferation and epithelial sodium channel (ENaC) activity. A number of reports have described various GILZ activities, focusing on a single isoform with molecular mass of ∼17 kDa, now termed GILZ1. In GILZ immunoblots using a newly developed antiserum, we detected multiple species in extracts from cultured kidney cells. Mass spectrometric analysis revealed that one of these represented a previously uncharacterized distinct isoform of GILZ, GILZ2. Rapid amplification of cDNA ends was used to clone cDNAs corresponding to four isoforms, which, in addition to GILZ1 and GILZ2, included new isoforms GILZ3 and GILZ4. Heterologous expression of these four GILZ isoforms in cultured cells revealed striking functional differences. Notably, GILZ1 was the only isoform that significantly stimulated ENaC-mediated Na+ current in a kidney collecting duct cell line, although GILZ2 and GILZ3 also stimulated ENaC surface expression in HEK 293 cells. GILZ1 and GILZ3, and to a lesser extent GILZ2, inhibited ERK phosphorylation. Interestingly, GILZ4, which had no effect on either ENaC or ERK, potently suppressed cellular proliferation, as did GILZ1, but not GILZ2 or GILZ3. Finally, rat and mouse tissues all expressed multiple GILZ species but varied in the relative abundance of each. These data suggest that multiple GILZ isoforms are expressed in most cells and tissues and that these play distinct roles in regulating key cellular functions, including proliferation and ion transport. Furthermore, GILZ inhibition of ERK appears to play an essential role in stimulation of cell surface ENaC but not in inhibition of proliferation.","claims":[{"public_id":"cl_37e5c8a7647b830dd7dee5f03ca329e3","status":"active","text":"GILZ1 and GILZ3, and to a lesser extent GILZ2, inhibited ERK phosphorylation.","confidence":0.92,"contributors":[{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["extraction"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ 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(ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_f8a22022f401ff321504e7f02124f56b"},{"public_id":"cl_af9c9c59d4bf949442246bf085623cfe","status":"active","text":"Mass spectrometric analysis identified GILZ2 as a previously uncharacterized distinct isoform of glucocorticoid-induced leucine zipper protein in cultured kidney cell extracts.","confidence":0.93,"contributors":[{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["extraction"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ 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