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Proc Natl Acad Sci U S A
2003 Jul 22;10015:8776-81. doi: 10.1073/pnas.1432696100.
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Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein.
Xie J
,
Lee JA
,
Kress TL
,
Mowry KL
,
Black DL
.
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The heterogeneous nuclear ribonucleoprotein particle (hnRNP) proteins play important roles in mRNA processing in eukaryotes, but little is known about how they are regulated by cellular signaling pathways. The polypyrimidine-tract binding protein (PTB, or hnRNP I) is an important regulator of alternative pre-mRNA splicing, of viral RNA translation, and of mRNA localization. Here we show that the nucleo-cytoplasmic transport of PTB is regulated by the 3',5'-cAMP-dependent protein kinase (PKA). PKA directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12 cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine mutation accumulates normally in the nucleus. However, export of this mutant protein from the nucleus is greatly reduced in heterokaryon shuttling assays. Conversely, hyperphosphorylation of PTB by coexpression with the catalytic subunit of PKA results in the accumulation of PTB in the cytoplasm. This accumulation is again specifically blocked by the S16A mutation. Similarly, in Xenopus oocytes, the phospho-Ser-16-PTB is restricted to the cytoplasm, whereas the non-Ser-16-phosphorylated PTB is nuclear. Thus, direct PKA phosphorylation of PTB at Ser-16 modulates the nucleo-cytoplasmic distribution of PTB. This phosphorylation likely plays a role in the cytoplasmic function of PTB.
Back,
Translation of polioviral mRNA is inhibited by cleavage of polypyrimidine tract-binding proteins executed by polioviral 3C(pro).
2002, Pubmed
Back,
Translation of polioviral mRNA is inhibited by cleavage of polypyrimidine tract-binding proteins executed by polioviral 3C(pro).
2002,
Pubmed
Beals,
Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3.
1997,
Pubmed
Black,
Activation of c-src neuron-specific splicing by an unusual RNA element in vivo and in vitro.
1992,
Pubmed
Borman,
The involvement of a spliceosome component in internal initiation of human rhinovirus RNA translation.
1993,
Pubmed
Boyle,
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
1991,
Pubmed
Briggs,
The cAMP-dependent protein kinase site (Ser312) enhances dorsal nuclear import through facilitating nuclear localization sequence/importin interaction.
1998,
Pubmed
Chou,
Multisite RNA binding and release of polypyrimidine tract binding protein during the regulation of c-src neural-specific splicing.
2000,
Pubmed
Cote,
A Xenopus protein related to hnRNP I has a role in cytoplasmic RNA localization.
1999,
Pubmed
,
Xenbase
Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase
Fan,
HNS, a nuclear-cytoplasmic shuttling sequence in HuR.
1998,
Pubmed
,
Xenbase
Feramisco,
Optimal spatial requirements for the location of basic residues in peptide substrates for the cyclic AMP-dependent protein kinase.
1980,
Pubmed
Ferrell,
Xenopus oocyte maturation: new lessons from a good egg.
1999,
Pubmed
,
Xenbase
Gauthier-Rouvière,
The serum response factor nuclear localization signal: general implications for cyclic AMP-dependent protein kinase activity in control of nuclear translocation.
1995,
Pubmed
Gray,
Regulation of ion channels by cAMP-dependent protein kinase and A-kinase anchoring proteins.
1998,
Pubmed
Görner,
Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity.
1998,
Pubmed
Habelhah,
ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation.
2001,
Pubmed
Ichikawa,
Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC12 cells.
2002,
Pubmed
Jans,
Nuclear targeting signal recognition: a key control point in nuclear transport?
2000,
Pubmed
Kamath,
Nucleocytoplasmic shuttling of polypyrimidine tract-binding protein is uncoupled from RNA export.
2001,
Pubmed
Kemp,
Protein kinase recognition sequence motifs.
1990,
Pubmed
Komeili,
Roles of phosphorylation sites in regulating activity of the transcription factor Pho4.
1999,
Pubmed
Krecic,
hnRNP complexes: composition, structure, and function.
1999,
Pubmed
Lai,
Cellular factors in the transcription and replication of viral RNA genomes: a parallel to DNA-dependent RNA transcription.
1998,
Pubmed
Li,
Characterization of the nuclear export signal of polypyrimidine tract-binding protein.
2002,
Pubmed
Markovtsov,
Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein.
2000,
Pubmed
Mattaj,
Nucleocytoplasmic transport: the soluble phase.
1998,
Pubmed
Meinkoth,
Signal transduction through the cAMP-dependent protein kinase.
1993,
Pubmed
Michael,
A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway.
1995,
Pubmed
Montminy,
Transcriptional regulation by cyclic AMP.
1997,
Pubmed
Nakielny,
Transport of proteins and RNAs in and out of the nucleus.
1999,
Pubmed
Niepmann,
Functional involvement of polypyrimidine tract-binding protein in translation initiation complexes with the internal ribosome entry site of foot-and-mouth disease virus.
1997,
Pubmed
Ohno,
PHAX, a mediator of U snRNA nuclear export whose activity is regulated by phosphorylation.
2000,
Pubmed
,
Xenbase
Pilipenko,
Cell-specific proteins regulate viral RNA translation and virus-induced disease.
2001,
Pubmed
Polydorides,
A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing.
2000,
Pubmed
Pérez,
Multiple RRMs contribute to RNA binding specificity and affinity for polypyrimidine tract binding protein.
1997,
Pubmed
Romanelli,
Importin alpha binds to an unusual bipartite nuclear localization signal in the heterogeneous ribonucleoprotein type I.
2002,
Pubmed
Romanelli,
Sequence determinants for hnRNP I protein nuclear localization.
1997,
Pubmed
Sanford,
Developmental regulation of SR protein phosphorylation and activity.
1999,
Pubmed
Sanford,
Regulation of SR protein localization during development.
2001,
Pubmed
Shipston,
Alternative splicing of potassium channels: a dynamic switch of cellular excitability.
2001,
Pubmed
Valcárcel,
Post-transcriptional regulation: the dawn of PTB.
1997,
Pubmed
Wagner,
Polypyrimidine tract binding protein antagonizes exon definition.
2001,
Pubmed
Xiao,
SV40 large tumor antigen nuclear import is regulated by the double-stranded DNA-dependent protein kinase site (serine 120) flanking the nuclear localization sequence.
1997,
Pubmed
Yun,
Conserved SR protein kinase functions in nuclear import and its action is counteracted by arginine methylation in Saccharomyces cerevisiae.
2000,
Pubmed
van der Houven van Oordt,
The MKK(3/6)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation.
2000,
Pubmed
