{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T20:25:24Z","timestamp":1781123124052,"version":"3.54.1"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,4,17]]},"abstract":"<jats:p>Incubation of permeabilized cells with mitotic extracts results in extensive fragmentation of the pericentriolarly organized stacks of cisternae. The fragmented Golgi membranes are subsequently dispersed from the pericentriolar region. We have shown previously that this process requires the cytosolic protein mitogen-activated protein kinase kinase 1 (MEK1). Extracellular signal\u2013regulated kinase (ERK) 1 and ERK2, the known downstream targets of MEK1, are not required for this fragmentation (Acharya et al. 1998). We now provide evidence that MEK1 is specifically phosphorylated during mitosis. The mitotically phosphorylated MEK1, upon partial proteolysis with trypsin, generates a different peptide population compared with interphase MEK1. MEK1 cleaved with the lethal factor of the anthrax toxin can still be activated by its upstream mitotic kinases, and this form is fully active in the Golgi fragmentation process. We believe that the mitotic phosphorylation induces a change in the conformation of MEK1 and that this form of MEK1 recognizes Golgi membranes as a target compartment. Immunoelectron microscopy analysis reveals that treatment of permeabilized normal rat kidney (NRK) cells with mitotic extracts, treated with or without lethal factor, converts stacks of pericentriolar Golgi membranes into smaller fragments composed predominantly of tubuloreticular elements. These fragments are similar in distribution, morphology, and size to the fragments observed in the prometaphase\/metaphase stage of the cell cycle in vivo.<\/jats:p>","DOI":"10.1083\/jcb.149.2.331","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"331-340","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":86,"title":["A Specific Activation of the Mitogen-Activated Protein Kinase Kinase 1 (Mek1) Is Required for Golgi Fragmentation during Mitosis"],"prefix":"10.1083","volume":"149","author":[{"given":"Antonino","family":"Colanzi","sequence":"first","affiliation":[{"name":"aDepartment of Biology, Department of Neurosciences, University of California San Diego, La Jolla, California 92093-0347"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Deerinck","sequence":"additional","affiliation":[{"name":"bNational Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, California 92093-0347"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Ellisman","sequence":"additional","affiliation":[{"name":"bNational Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, California 92093-0347"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Malhotra","sequence":"additional","affiliation":[{"name":"aDepartment of Biology, Department of Neurosciences, University of California San Diego, La Jolla, California 92093-0347"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,4,17]]},"reference":[{"key":"2023072905322832700_Acharyaetal1998","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0092-8674(00)80913-7","article-title":"Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis","volume":"92","author":"Acharya","year":"1998","journal-title":"Cell."},{"key":"2023072905322832700_Alessietal1994","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1002\/j.1460-2075.1994.tb06424.x","article-title":"Identification of the sites in MAP kinase kinase-1 phosphorylated by p74Raf-1","volume":"13","author":"Alessi","year":"1994","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072905322832700_Alessietal1995","doi-asserted-by":"crossref","first-page":"27489","DOI":"10.1074\/jbc.270.46.27489","article-title":"PD is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo","volume":"270","author":"Alessi","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2023072905322832700_Collas1999","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1242\/jcs.112.6.977","article-title":"Sequential PKC- and cdc2-mediated phosphorylation events elicit zebrafish nuclear envelope disassembly","volume":"112","author":"Collas","year":"1999","journal-title":"J. Cell Sci."},{"key":"2023072905322832700_Crewsetal1992","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1126\/science.1411546","article-title":"The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product","volume":"258","author":"Crews","year":"1992","journal-title":"Science."},{"key":"2023072905322832700_Dudleyetal1995","doi-asserted-by":"crossref","first-page":"7686","DOI":"10.1073\/pnas.92.17.7686","article-title":"A synthetic inhibitor of the mitogen activated protein kinase cascade","volume":"92","author":"Dudley","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072905322832700_Duesberyetal1998","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1126\/science.280.5364.734","article-title":"Proteolytic inactivation of MAP kinase kinase by anthrax lethal factor","volume":"280","author":"Duesbery","year":"1998","journal-title":"Science."},{"key":"2023072905322832700_HiroseandKomamine1989","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1469-8137.1989.tb02353.x","article-title":"Changes in the ultrastructure of Golgi apparatus during the cell cycle in synchronous cultures of catharanthus roseus","volume":"111","author":"Hirose","year":"1989","journal-title":"New Phytol."},{"key":"2023072905322832700_JeschandLinstedt1998","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1091\/mbc.9.3.623","article-title":"The Golgi and endoplasmic reticulum remain independent during mitosis in HeLa cells","volume":"9","author":"Jesch","year":"1998","journal-title":"Mol. Biol. Cell."},{"key":"2023072905322832700_Loweetal1998","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0092-8674(00)81737-7","article-title":"Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis","volume":"94","author":"Lowe","year":"1998","journal-title":"Cell."},{"key":"2023072905322832700_Lucocq1992","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1242\/jcs.103.4.875","article-title":"Mimicking mitotic Golgi disassembly using okadaic acid","volume":"103","author":"Lucocq","year":"1992","journal-title":"J. Cell Sci."},{"key":"2023072905322832700_Lucocqetal1987","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1083\/jcb.104.4.865","article-title":"A mitotic form of the Golgi apparatus in HeLa cells","volume":"104","author":"Lucocq","year":"1987","journal-title":"J. Cell Biol."},{"key":"2023072905322832700_Lucocqetal1995","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1006\/jsbi.1995.1056","article-title":"The pathway of Golgi cluster formation in okadaic acid treated cells","volume":"115","author":"Lucocq","year":"1995","journal-title":"J. Struct. Biol."},{"key":"2023072905322832700_MorenoandNurse1990","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/0092-8674(90)90463-O","article-title":"Substrates for p34cdc2. In vivo veritas?","volume":"61","author":"Moreno","year":"1990","journal-title":"Cell."},{"key":"2023072905322832700_Polishchuketal1999","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S0171-9335(99)80096-X","article-title":"Coalescence of Golgi fragments in microtubule-deprived living cells","volume":"78","author":"Polishchuk","year":"1999","journal-title":"Eur. J. Cell Biol."},{"key":"2023072905322832700_Preussetal1992","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1091\/mbc.3.7.789","article-title":"Characterization of the Saccharomyces Golgi complex through the cell cycle by immunoelectron microscopy","volume":"3","author":"Preuss","year":"1992","journal-title":"Mol. Biol. Cell."},{"key":"2023072905322832700_RobbinsandGonatas1964","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1083\/jcb.21.3.429","article-title":"The ultrastructure of a mammalian cell during the mitotic cycle","volume":"21","author":"Robbins","year":"1964","journal-title":"J. Cell Biol."},{"key":"2023072905322832700_RobinsonandCobb1997","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0955-0674(97)80061-0","article-title":"Mitogen-activated protein kinase pathways","volume":"9","author":"Robinson","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"2023072905322832700_Rossomondoetal1994","first-page":"1594","article-title":"Mitogen activated protein kinase kinase 1 (MEK1) is negatively regulated by threonine phosphorylation","volume":"14","author":"Rossomondo","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"2023072905322832700_Sessoetal1999","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1054\/tice.1999.0042","article-title":"Structural elements common to mitosis and apoptosis","volume":"31","author":"Sesso","year":"1999","journal-title":"Tissue Cell."},{"key":"2023072905322832700_Shapiroetal1998","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1083\/jcb.142.6.1533","article-title":"Activation of the MKK\/ERK pathway during somatic cell mitosisdirect interactions of active ERK with kinetochores and regulation of the mitotic 3F3\/2 phosphoantigen","volume":"142","author":"Shapiro","year":"1998","journal-title":"J. Cell Biol."},{"key":"2023072905322832700_Stanleyetal1997","doi-asserted-by":"crossref","first-page":"14467","DOI":"10.1073\/pnas.94.26.14467","article-title":"The mechanism of Golgi segregation during mitosis is cell type specific","volume":"94","author":"Stanley","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072905322832700_Takizawaetal1993","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/0092-8674(93)90638-7","article-title":"Complete vesiculation of Golgi membranes and inhibition of protein transport by a novel sea sponge metabolite, ilimaquinone","volume":"73","author":"Takizawa","year":"1993","journal-title":"Cell."},{"key":"2023072905322832700_ThybergandMoskalewski1992","first-page":"495","article-title":"Reorganization of the Golgi complex in association with mitosisredistribution to the endoplasmic reticulum and effects of brefeldin A","volume":"24","author":"Thyberg","year":"1992","journal-title":"J. Submicrosc. Cytol. Pathol."},{"key":"2023072905322832700_Vitaleetal1998","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1006\/bbrc.1998.9040","article-title":"Anthrax lethal factor cleaves the N-terminus of MAPKKs and indices tyrosine\/threonine phosphorylation of MAPKs in cultured macrophages","volume":"248","author":"Vitale","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023072905322832700_Wangetal1997","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1083\/jcb.137.2.433","article-title":"A role for mitogen activated kinase in the spindle assembly checkpoint in XTC cells","volume":"137","author":"Wang","year":"1997","journal-title":"J. Cell Biol."},{"key":"2023072905322832700_Warren1993","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.bi.62.070193.001543","article-title":"Membrane partitioning during cell division","volume":"62","author":"Warren","year":"1993","journal-title":"Annu. Rev. Biochem."},{"key":"2023072905322832700_Wrightetal1999","doi-asserted-by":"crossref","first-page":"11335","DOI":"10.1073\/pnas.96.20.11335","article-title":"Mitogen-activated protein kinase kinase activity is required for the G(2)\/M transition of the cell cycle in mammalian fibroblasts","volume":"28","author":"Wright","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072905322832700_Zaaletal1999","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0092-8674(00)81548-2","article-title":"Golgi membranes are absorbed into and reemerge from the ER during mitosis","volume":"99","author":"Zaal","year":"1999","journal-title":"Cell."},{"key":"2023072905322832700_Zecevicetal1998","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1083\/jcb.142.6.1547","article-title":"Active MAP kinase in mitosislocalization at kinetochores and association with the motor protein CENP-E","volume":"142","author":"Zecevic","year":"1998","journal-title":"J. Cell Biol."}],"container-title":["The Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/149\/2\/331\/1870221\/9912097.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/149\/2\/331\/1870221\/9912097.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T05:33:14Z","timestamp":1690608794000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/149\/2\/331\/32115\/A-Specific-Activation-of-the-Mitogen-Activated"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,4,17]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2000,4,17]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.149.2.331","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,4,17]]}}}