Nerve growth factor controls GAP-43 mRNA stability via the phosphoprotein ARPP-19.
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.
Irwin
Nina
N
Department of Neurosurgery, Children's Hospital, Boston, MA 02115, USA.
Chao
Steven
S
Goritchenko
Luda
L
Horiuchi
Atsuko
A
Greengard
Paul
P
Nairn
Angus C
AC
Benowitz
Larry I
LI
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019922:GAP-43 Protein / Q000235:genetics*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction
D019922:GAP-43 Protein; D010750:Phosphoproteins; D012333:RNA, Messenger; C064321:cyclic AMP-regulated phosphoprotein 19; D012694:Serine; D020932:Nerve Growth Factor