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Nerve Growth Factor Controls GAP-43 mRNA Stability Via the Phosphoprotein ARPP-19

Nina Irwin, Steven Chao, Luda Goritchenko, Atsuko Horiuchi, Paul Greengard, Angus C. Nairn and Larry I. Benowitz
Proceedings of the National Academy of Sciences of the United States of America
Vol. 99, No. 19 (Sep. 17, 2002), pp. 12427-12431
Stable URL: http://www.jstor.org/stable/3073231
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Nerve Growth Factor Controls GAP-43 mRNA Stability Via the Phosphoprotein ARPP-19
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Abstract

The membrane phosphoprotein GAP-43 is involved in axon growth and synaptic plasticity. In PC12 pheochromocytoma cells, induction of a neuronal phenotype by nerve growth factor (NGF) is accompanied by a marked increase in GAP-43 levels. NGF regulates GAP-43 expression by altering the half-life of its mRNA. We report here that the phosphoprotein ARPP-19 mediates this regulation. In an NGF-dependent manner, ARPP-19 bound to a region in the 3′ end of GAP-43 mRNA previously found to be important for regulating the half-life of the mRNA. Overexpression of wild-type ARPP-19 in PC12 cells increased the NGF-dependent expression of a reporter construct linked to the critical 3′ region of GAP-43 mRNA. Mutation of serine 104, the site of phosphorylation by protein kinase A in ARPP-19, to either alanine or aspartate abolished this regulation in PC12 cells. These findings demonstrate that ARPP-19 is an important link between NGF signaling and post-transcriptional control of neuronal gene expression.

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