The MKK3/6-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation

van Oordt, W. V., Diaz-Meco, M. T., Lozano, J., Krainer, A. R., Moscat, J., Caceres, J. F. (April 2000) The MKK3/6-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation. Journal of Cell Biology, 149 (2). pp. 307-316. ISSN 0021-9525

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10769024
DOI: 10.1083/jcb.149.2.307

Abstract

Individual members of the serine-arginine (SR) and heterogeneous nuclear ribonucleoprotein (hnRNP) A/B families of proteins have antagonistic effects in regulating alternative splicing. Although hnRNP Al accumulates predominantly in the nucleus, it shuttles continuously between the nucleus and the cytoplasm. Some but not all SR proteins also undergo nucleo-cytoplasmic shuttling, which is affected by phosphorylation of their serine/arginine (RS)-rich domain. The signaling mechanisms that control the subcellular localization of these proteins are unknown. We show that exposure of NIH-3T3 and SV-40 transformed green monkey kidney (COS) cells to stress stimuli such as osmotic shock or UVC irradiation, but not to mitogenic activators such as PDGF or EGF, results in a marked cytoplasmic accumulation of hnRNP Al, concomitant with an increase in its phosphorylation. These effects are mediated by the MKK3/6-p38 pathway, and moreover, p38 activation is necessary and sufficient for the induction of hnRNP Al cytoplasmic accumulation. The stress-induced increase in the cytoplasmic levels of hnRNP A/B proteins and the concomitant decrease in their nuclear abundance are paralleled by changes in the alternative splicing pattern of an adenovirus E1A pre-mRNA splicing reporter. These results suggest the intriguing possibility that signaling mechanisms regulate pre-mRNA splicing in vivo by influencing the subcellular distribution of splicing factors.

Item Type: Paper
Uncontrolled Keywords: alternative splicing hnRNP A1 signal transduction p38 kinase stress signaling rna-binding-proteins signal-transduction pathway osmotic response element aldose reductase gene kinase-c-zeta messenger-rna nuclear export in-vivo mapkap kinase-2 sr proteins
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > nuclear ribonucleoprotein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation > transduction
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation > transduction
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: April 2000
Date Deposited: 11 Dec 2013 20:08
Last Modified: 11 Dec 2013 20:08
PMCID: PMC2175157
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28915

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