{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T07:15:29Z","timestamp":1774768529122,"version":"3.50.1"},"reference-count":32,"publisher":"Proceedings of the National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,11,25]]},"abstract":"<jats:p>\n            3\u2032-Phosphoinositide-dependent protein kinase 1 (PDK-1) phosphorylates and activates members of the AGC protein kinase family and plays an important role in the regulation of cell survival, differentiation, and proliferation. However, how PDK-1 is regulated in cells remains elusive. In this study, we demonstrated that PDK-1 can shuttle between the cytoplasm and nucleus. Treatment of cells with leptomycin B, a nuclear export inhibitor, results in a nuclear accumulation of PDK-1. PDK-1 nuclear localization is increased by insulin, and this process is inhibited by pretreatment of cells with phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. Consistent with the idea that PDK-1 nuclear translocation is regulated by the PI3-kinase signaling pathway, PDK-1 nuclear localization is increased in cells deficient of PTEN (phosphatase and tensin homologue deleted on chromosome 10). Deletion mapping and mutagenesis studies unveiled that presence of a functional nuclear export signal (NES) in mouse PDK-1 located at amino acid residues 382 to 391. Overexpression of constitutively nuclear PDK-1, which retained autophosphorylation at Ser-244 in the activation loop in cells and its kinase activity\n            <jats:italic>in vitro<\/jats:italic>\n            , led to increased phosphorylation of the predominantly nuclear PDK-1 substrate p70 S6K\u03b2I. However, the ability of constitutively nuclear PDK-1 to induce anchorage-independent growth and to protect against UV-induced apoptosis is greatly diminished compared with the wild-type enzyme. Taken together, these findings suggest that nuclear translocation may be a mechanism to sequestrate PDK-1 from activation of the cytosolic signaling pathways and that this process may play an important role in regulating PDK-1-mediated cell signaling and function.\n          <\/jats:p>","DOI":"10.1073\/pnas.2335486100","type":"journal-article","created":{"date-parts":[[2003,11,25]],"date-time":"2003-11-25T20:59:06Z","timestamp":1069793946000},"page":"14006-14011","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Nuclear translocation of 3\u2032-phosphoinositide-dependent protein kinase 1 (PDK-1): A potential regulatory mechanism for PDK-1 function"],"prefix":"10.1073","volume":"100","author":[{"given":"Mei A.","family":"Lim","sequence":"first","affiliation":[{"name":"Departments of Pharmacology, Biochemistry, and Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229"}]},{"given":"Chintan K.","family":"Kikani","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Biochemistry, and Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229"}]},{"given":"Michael J.","family":"Wick","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Biochemistry, and Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229"}]},{"given":"Lily Q.","family":"Dong","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Biochemistry, and Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229"}]}],"member":"341","published-online":{"date-parts":[[2003,11,17]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(06)00122-9"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70037-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5351.707"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2001.00479.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202894"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3460561"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568005310101030209"},{"key":"e_1_3_2_8_2","first-page":"3538","volume":"62","year":"2002","unstructured":"Zeng, X., Xu, H. & Glazer, R. 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