|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 35, 22745-22752, August 28, 1998
From the Nuclear Signaling Laboratory, Division of Biochemistry and
Molecular Biology, John Curtin School of Medical Research, Canberra
City, A.C.T. 2601, Australia and Control over the nuclear import of transcription
factors (TFs) represents a level of gene regulation integral to
cellular processes such as differentiation and transformation. The
Drosophila TF Dorsal shares with other rel TF
family members the fact that it contains a phosphorylation site for the
cAMP-dependent protein kinase (PKA) 22 amino acids
N-terminal to the nuclear localization signal (NLS) at amino acids
335-340. This study examines for the first time the nuclear import
kinetics of Dorsal fusion proteins in rat hepatoma cells in
vivo and in vitro. Nuclear uptake was found to be not
only NLS-dependent, but also strongly dependent on the PKA
site, whereby substitution of Ser312 by either Ala or Glu
using site-directed mutagenesis severely reduced nuclear accumulation.
Exogenous cAMP or PKA catalytic subunit significantly enhanced the
nuclear import of wild-type proteins both in vivo and
in vitro. Using a direct binding assay, the molecular basis
of PKA site enhancement of Dorsal fusion protein nuclear import was
determined to be PKA site-mediated modulation of NLS recognition by the
importin 58/97 complex. The physiological relevance of these results is
supported by the observation that Drosophila embryos
expressing PKA site Dorsal mutant variants were impaired in
development. We conclude that the Dorsal NLS and PKA site constitute a
phosphorylation-regulated NLS essential to Dorsal function and able to
function in heterologous mammalian cell systems, where phosphorylation
modulates the affinity of NLS recognition by importin.
The cAMP-dependent Protein Kinase Site
(Ser312) Enhances Dorsal Nuclear Import through
Facilitating Nuclear Localization Sequence/Importin Interaction
,, Department of Molecular
Genetics, Albert Einstein College of Medicine,
New York, New York 10461
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Ghildyal, B. Jordan, D. Li, H. Dagher, P. G. Bardin, J. E. Gern, and D. A. Jans Rhinovirus 3C Protease Can Localize in the Nucleus and Alter Active and Passive Nucleocytoplasmic Transport J. Virol., July 15, 2009; 83(14): 7349 - 7352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kuwahara, M. Nishizaki, and H. Kanazawa Nuclear Localization Signal and Phosphorylation of Serine350 Specify Intracellular Localization of DRAK2 J. Biochem., March 1, 2008; 143(3): 349 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Youn and J.-S. Shin Nucleocytoplasmic Shuttling of HMGB1 Is Regulated by Phosphorylation That Redirects It toward Secretion J. Immunol., December 1, 2006; 177(11): 7889 - 7897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Citterio, H. D. Jones, G. Pacheco-Rodriguez, A. Islam, J. Moss, and M. Vaughan Effect of protein kinase A on accumulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei PNAS, February 21, 2006; 103(8): 2683 - 2688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Faul, S. Huttelmaier, J. Oh, V. Hachet, R. H. Singer, and P. Mundel Promotion of importin {alpha}-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3 J. Cell Biol., May 9, 2005; 169(3): 415 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Soboleva, D. A. Jans, M. Johnson-Saliba, and R. T. Baker Nuclear-Cytoplasmic Shuttling of the Oncogenic Mouse UNP/USP4 Deubiquitylating Enzyme J. Biol. Chem., January 7, 2005; 280(1): 745 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Ullas and M. R. S. Rao Phosphorylation of Rat Spermatidal Protein TP2 by Sperm-specific Protein Kinase A and Modulation of Its Transport into the Haploid Nucleus J. Biol. Chem., December 26, 2003; 278(52): 52673 - 52680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xie, J.-A. Lee, T. L. Kress, K. L. Mowry, and D. L. Black Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein PNAS, July 22, 2003; 100(15): 8776 - 8781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. M. Fontes, T. Teh, D. Jans, R. I. Brinkworth, and B. Kobe Structural Basis for the Specificity of Bipartite Nuclear Localization Sequence Binding by Importin-{alpha} J. Biol. Chem., July 18, 2003; 278(30): 27981 - 27987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Millholland, J. M. Fitch, C. X. Cai, E. P. Gibney, K. E. Beazley, and T. F. Linsenmayer Ferritoid, a Tissue-specific Nuclear Transport Protein for Ferritin in Corneal Epithelial Cells J. Biol. Chem., June 20, 2003; 278(26): 23963 - 23970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Schedlich, T. Nilsen, A. P. John, D. A. Jans, and R. C. Baxter Phosphorylation of Insulin-Like Growth Factor Binding Protein-3 by Deoxyribonucleic Acid-Dependent Protein Kinase Reduces Ligand Binding and Enhances Nuclear Accumulation Endocrinology, May 1, 2003; 144(5): 1984 - 1993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Jones, M. Luo, M. Peters-Golden, and T. G. Brock Identification of Two Novel Nuclear Import Sequences on the 5-Lipoxygenase Protein J. Biol. Chem., March 14, 2003; 278(12): 10257 - 10263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chua, C. Lingner, C. Frazer, and P. G. Young The sal3+ Gene Encodes an Importin-{beta} Implicated in the Nuclear Import of Cdc25 in Schizosaccharomyces pombe Genetics, October 1, 2002; 162(2): 689 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Brooks, M. Johansson, A. V. John, Y. Xu, D. A. Jans, and S. G. Vasudevan The Interdomain Region of Dengue NS5 Protein That Binds to the Viral Helicase NS3 Contains Independently Functional Importin beta 1 and Importin alpha /beta -Recognized Nuclear Localization Signals J. Biol. Chem., September 20, 2002; 277(39): 36399 - 36407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Forwood, V. Harley, and D. A. Jans The C-terminal Nuclear Localization Signal of the Sex-determining Region Y (SRY) High Mobility Group Domain Mediates Nuclear Import through Importin beta 1 J. Biol. Chem., November 30, 2001; 276(49): 46575 - 46582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Bird, E. J. Blink, C. E. Hirst, M. S. Buzza, P. M. Steele, J. Sun, D. A. Jans, and P. I. Bird Nucleocytoplasmic Distribution of the Ovalbumin Serpin PI-9 Requires a Nonconventional Nuclear Import Pathway and the Export Factor Crm1 Mol. Cell. Biol., August 15, 2001; 21(16): 5396 - 5407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Butcher, L. Kim, P. F. Johnson, and E. Y. Denkers Toxoplasma gondii Tachyzoites Inhibit Proinflammatory Cytokine Induction in Infected Macrophages by Preventing Nuclear Translocation of the Transcription Factor NF-{kappa}B J. Immunol., August 15, 2001; 167(4): 2193 - 2201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Uv, P. Roth, N. Xylourgidis, A. Wickberg, R. Cantera, and C. Samakovlis members only encodes a Drosophila nucleoporin required for Rel protein import and immune response activation Genes & Dev., August 1, 2000; 14(15): 1945 - 1957. [Abstract] [Full Text]
|
|
|
|
|
|
E. Vielhaber, E. Eide, A. Rivers, Z.-H. Gao, and D. M. Virshup Nuclear Entry of the Circadian Regulator mPER1 Is Controlled by Mammalian Casein Kinase I varepsilon Mol. Cell. Biol., July 1, 2000; 20(13): 4888 - 4899. [Abstract] [Full Text]
|
|
|
|
|
|
S. Hubner, H. M. S. Smith, W. Hu, C. K. Chan, H.-P. Rihs, B. M. Paschal, N. V. Raikhel, and D. A. Jans Plant Importin alpha Binds Nuclear Localization Sequences with High Affinity and Can Mediate Nuclear Import Independent of Importin beta J. Biol. Chem., August 6, 1999; 274(32): 22610 - 22617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hu and D. A. Jans Efficiency of Importin alpha /beta -Mediated Nuclear Localization Sequence Recognition and Nuclear Import. DIFFERENTIAL ROLE OF NTF2 J. Biol. Chem., May 28, 1999; 274(22): 15820 - 15827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abu-Shaar, H. D. Ryoo, and R. S. Mann Control of the nuclear localization of Extradenticle by competing nuclear import and export signals Genes & Dev., April 15, 1999; 13(8): 935 - 945. [Abstract] [Full Text]
|
|
|
|
|
|
M. H. C. Lam, L. J. Briggs, W. Hu, T. J. Martin, M. T. Gillespie, and D. A. Jans Importin beta Recognizes Parathyroid Hormone-related Protein with High Affinity and Mediates Its Nuclear Import in the Absence of Importin alpha J. Biol. Chem., March 12, 1999; 274(11): 7391 - 7398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Drier, L. H. Huang, and R. Steward Nuclear import of the Drosophila Rel protein Dorsal is regulated by phosphorylation Genes & Dev., March 1, 1999; 13(5): 556 - 568. [Abstract] [Full Text]
|
|
|
|
|
|
B. Catimel, T. Teh, M. R. M. Fontes, I. G. Jennings, D. A. Jans, G. J. Howlett, E. C. Nice, and B. Kobe Biophysical Characterization of Interactions Involving Importin-alpha during Nuclear Import J. Biol. Chem., August 31, 2001; 276(36): 34189 - 34198. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |