{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T20:51:57Z","timestamp":1770497517506,"version":"3.49.0"},"reference-count":46,"publisher":"Proceedings of the National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,7,22]]},"abstract":"<jats:p>\n            The heterogeneous nuclear ribonucleoprotein particle (hnRNP) proteins play\n important roles in mRNA processing in eukaryotes, but little is known about\n how they are regulated by cellular signaling pathways. The\n polypyrimidine-tract binding protein (PTB, or hnRNP I) is an important\n regulator of alternative pre-mRNA splicing, of viral RNA translation, and of\n mRNA localization. Here we show that the nucleo-cytoplasmic transport of PTB\n is regulated by the 3\u2032,5\u2032-cAMP-dependent protein kinase (PKA). PKA\n directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12\n cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine\n mutation accumulates normally in the nucleus. However, export of this mutant\n protein from the nucleus is greatly reduced in heterokaryon shuttling assays.\n Conversely, hyperphosphorylation of PTB by coexpression with the catalytic\n subunit of PKA results in the accumulation of PTB in the cytoplasm. This\n accumulation is again specifically blocked by the S16A mutation. Similarly, in\n            <jats:italic>Xenopus<\/jats:italic>\n            oocytes, the phospho-Ser-16-PTB is restricted to the\n cytoplasm, whereas the non-Ser-16-phosphorylated PTB is nuclear. Thus, direct\n PKA phosphorylation of PTB at Ser-16 modulates the nucleo-cytoplasmic\n distribution of PTB. This phosphorylation likely plays a role in the\n cytoplasmic function of PTB.\n          <\/jats:p>","DOI":"10.1073\/pnas.1432696100","type":"journal-article","created":{"date-parts":[[2003,7,22]],"date-time":"2003-07-22T19:39:06Z","timestamp":1058902746000},"page":"8776-8781","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":148,"title":["Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein"],"prefix":"10.1073","volume":"100","author":[{"given":"Jiuyong","family":"Xie","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute,\r Department of Microbiology, Immunology, and\r Molecular Genetics, University of California, Los Angeles, CA 90095-1662; and\r Department of Molecular Biology, Cell Biology,\r and Biochemistry, Brown University, Providence, RI 02912"}]},{"given":"Ji-Ann","family":"Lee","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute,\r Department of Microbiology, Immunology, and\r Molecular Genetics, University of California, Los Angeles, CA 90095-1662; and\r Department of Molecular Biology, Cell Biology,\r and Biochemistry, Brown University, Providence, RI 02912"}]},{"given":"Tracy L.","family":"Kress","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute,\r Department of Microbiology, Immunology, and\r Molecular Genetics, University of California, Los Angeles, CA 90095-1662; and\r Department of Molecular Biology, Cell Biology,\r and Biochemistry, Brown University, Providence, RI 02912"}]},{"given":"Kimberly L.","family":"Mowry","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute,\r Department of Microbiology, Immunology, and\r Molecular Genetics, University of California, Los Angeles, CA 90095-1662; and\r Department of Molecular Biology, Cell Biology,\r and Biochemistry, Brown University, Providence, RI 02912"}]},{"given":"Douglas L.","family":"Black","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute,\r Department of Microbiology, Immunology, and\r Molecular Genetics, University of California, Los Angeles, CA 90095-1662; and\r Department of Molecular Biology, Cell Biology,\r and Biochemistry, Brown University, Providence, RI 02912"}]}],"member":"341","published-online":{"date-parts":[[2003,7,8]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80051-9"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.265"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81666-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35060131"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.2.307"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(06)00361-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.10.3281-3288.2001"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9098"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-74-9-1775"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8330-8339.1997"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.23.6899"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80345-7"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9711745"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3677"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.02942.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109686200"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.12.3808"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01076769"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.66.1.807"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02068-2"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(98)80057-3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.35.22745"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.4.586"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.1.433"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90291-J"},{"key":"e_1_3_2_26_2","unstructured":"Rosenberg I. 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(1996) in Protein Analysis\n and Purification: Benchtop Techniques (Birkhauser New York) pp.\n 226\u2013227."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)01013-R"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051360203"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80260-9"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85658-2"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(90)90073-K"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110128397"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.20.7463-7479.2000"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(199910)21:10<833::AID-BIES5>3.0.CO;2-P"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.35.22191"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5416.977"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5308.1930"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(200006)22:6<532::AID-BIES6>3.0.CO;2-O"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90119-1"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15293"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.4.707"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181340498"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.12.1513"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80829-6"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2529-2542.2002"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a003176"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1432696100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T01:29:12Z","timestamp":1650936552000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1432696100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,7,8]]},"references-count":46,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2003,7,22]]}},"alternative-id":["10.1073\/pnas.1432696100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1432696100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,7,8]]},"assertion":[{"value":"2003-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-07-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}