Abstract
hnRNP A1 is a nucleocytoplasmic shuttling protein that is involved in many aspects of mRNA metabolism. We have previously shown that activation of the p38 stress-signaling pathway in mammalian cells results in both hyperphosphorylation and cytoplasmic accumulation of hnRNP A1, affecting alternative splicing regulation in vivo. Here we show that the stress-induced cytoplasmic accumulation of hnRNP A1 occurs in discrete phase-dense particles, the cytoplasmic stress granules (SGs). Interestingly, mRNA-binding activity is required for both phosphorylation of hnRNP A1 and localization to SGs. We also show that these effects are mediated by the Mnk1/2 protein kinases that act downstream of p38. Finally, depletion of hnRNP A1 affects the recovery of cells from stress, suggesting a physiologically significant role for hnRNP A1 in the stress response. Our data are consistent with a model whereby hnRNP A1 recruitment to SGs involves Mnk1/2-dependent phosphorylation of mRNA-bound hnRNP A1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Survival
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Cytoplasmic Granules / metabolism*
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Enzyme Activation
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HeLa Cells
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Heterogeneous Nuclear Ribonucleoprotein A1
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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NIH 3T3 Cells
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Oxidative Stress*
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Peptides / genetics
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Peptides / metabolism
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Phosphorylation
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Poly(A)-Binding Protein I / genetics
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Poly(A)-Binding Protein I / metabolism
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Poly(A)-Binding Proteins / genetics
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Poly(A)-Binding Proteins / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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RNA Interference
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RNA, Messenger / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology
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T-Cell Intracellular Antigen-1
Substances
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Heterogeneous Nuclear Ribonucleoprotein A1
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Heterogeneous-Nuclear Ribonucleoprotein Group A-B
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Intracellular Signaling Peptides and Proteins
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Peptides
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Poly(A)-Binding Protein I
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Poly(A)-Binding Proteins
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RNA, Messenger
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Recombinant Fusion Proteins
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T-Cell Intracellular Antigen-1
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TIA1 protein, human
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MKNK1 protein, human
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MKNK2 protein, human
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Protein Serine-Threonine Kinases