{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:34:13Z","timestamp":1779330853656,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Translational control mediated by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2\u03b1) is central to stress-induced programs of gene expression. Trypanosomatids, important human pathogens, display differentiation processes elicited by contact with the distinct physiological milieu found in their insect vectors and mammalian hosts, likely representing stress situations.\n            <jats:italic>Trypanosoma brucei<\/jats:italic>\n            , the agent of African trypanosomiasis, encodes three potential eIF2\u03b1 kinases (TbeIF2K1 to -K3). We show here that TbeIF2K2 is a transmembrane glycoprotein expressed both in procyclic and in bloodstream forms. The catalytic domain of TbeIF2K2 phosphorylates yeast and mammalian eIF2\u03b1 at Ser51. It also phosphorylates the highly unusual form of eIF2\u03b1 found in trypanosomatids specifically at residue Thr169 that corresponds to Ser51 in other eukaryotes.\n            <jats:italic>T. brucei<\/jats:italic>\n            eIF2\u03b1, however, is not a substrate for GCN2 or PKR in vitro. The putative regulatory domain of TbeIF2K2 does not share any sequence similarity with known eIF2\u03b1 kinases. In both procyclic and bloodstream forms TbeIF2K2 is mainly localized in the membrane of the flagellar pocket, an organelle that is the exclusive site of exo- and endocytosis in these parasites. It can also be detected in endocytic compartments but not in lysosomes, suggesting that it is recycled between endosomes and the flagellar pocket. TbeIF2K2 location suggests a relevance in sensing protein or nutrient transport in\n            <jats:italic>T. brucei<\/jats:italic>\n            , an organism that relies heavily on posttranscriptional regulatory mechanisms to control gene expression in different environmental conditions. This is the first membrane-associated eIF2\u03b1 kinase described in unicellular eukaryotes.\n          <\/jats:p>","DOI":"10.1128\/ec.00249-07","type":"journal-article","created":{"date-parts":[[2007,9,15]],"date-time":"2007-09-15T01:04:22Z","timestamp":1189818262000},"page":"1979-1991","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Novel Membrane-Bound eIF2\u03b1 Kinase in the Flagellar Pocket of\n            <i>Trypanosoma brucei<\/i>"],"prefix":"10.1128","volume":"6","author":[{"given":"Maria Carolina S.","family":"Moraes","sequence":"first","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa C. L.","family":"Jesus","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilce N.","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhusudan","family":"Dey","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane S.","family":"Alves","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla C.","family":"Avila","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James D.","family":"Bangs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E.","family":"Dever","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Schenkman","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz A.","family":"Castilho","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.16.3253"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.105.4.1101"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112642"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35014014"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(98)00151-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.11.3611"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409311200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.8.1881"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.044"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00642-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4616"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90193-G"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.041"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.8.3063-3075.2005"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112631"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.323404"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02327"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2004.00234.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(03)00092-4"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.23.6909"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.8.7768349"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00105-9"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020556"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.35.21661"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb01947.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112680"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041164"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413660200"},{"key":"e_1_3_2_30_2","first-page":"503","year":"2000","unstructured":"Kaufman, R. J. 2000. The double-stranded RNA-activated protein kinase PKR, p. 503-527. In N. Sonenberg, J. W. B. Hershey, and M. B. Mathews (ed.), Translational control of gene expression. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.","journal-title":"Translational control of gene expression"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0561"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.45.32198"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200903200"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2003.10.016"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507511200"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.320090705"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402228200"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.13.4347-4368.2001"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.12.3.1218-1225.1992"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408571200"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.6.1425"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02667"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)94004-V"},{"key":"e_1_3_2_44_2","first-page":"10","volume":"122","year":"1989","unstructured":"Sikorsky, R. S., and P. Hieter. 1989. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics122:10-27.","journal-title":"Genetics"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3460281"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20040262"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3470703"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.14.3728"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.5.615"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.110.21.2661"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400541101"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.8.2706-2717.2000"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.20.7134-7146.2002"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.19.6681-6688.2002"}],"container-title":["Eukaryotic Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/EC.00249-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/EC.00249-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T14:14:15Z","timestamp":1645625655000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/EC.00249-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11]]},"references-count":53,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["10.1128\/EC.00249-07"],"URL":"https:\/\/doi.org\/10.1128\/ec.00249-07","relation":{},"ISSN":["1535-9778","1535-9786"],"issn-type":[{"value":"1535-9778","type":"print"},{"value":"1535-9786","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11]]},"assertion":[{"value":"2007-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-09-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}