Abstract
Treatment of 8-Br-cAMP promotes neurite outgrowth and neuronal differentiation in N1E115 mouse neuroblastoma cells. Prior or simultaneous treatment of PMA blocks 8-Br-cAMP-mediated neurite outgrowth. Phosphorylation of cellular proteins during these treatments was examined in a permeabilized cell system. While PMA promotes phosphorylation of the heat-stable protein kinase C substrates MARCKS and neuromodulin, 8-Br-cAMP hastens the dephosphorylation of a protein of M(r)95k (p95). Extensively purified, N-terminal sequenced, and judged from its phosphorylation properties, p95 was identified as the eukaryotic elongation factor-2 (eEF-2), whose dephosphorylation has been reported to be related to an increase in protein synthesis. It is likely 8-Br-cAMP stimulates dephosphorylation of eEf-2, promotes protein synthesis that eventually leads to neuronal differentiation in N1E115 cells.
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Amino Acid Sequence
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Animals
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Cell Differentiation / drug effects
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Mice
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Molecular Sequence Data
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Molecular Weight
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neuroblastoma / metabolism*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Peptide Elongation Factor 2
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Peptide Elongation Factors / chemistry
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Peptide Elongation Factors / genetics
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Peptide Elongation Factors / metabolism*
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Phosphorylation
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Protein Kinase C / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
Substances
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Nerve Tissue Proteins
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Peptide Elongation Factor 2
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Peptide Elongation Factors
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Phosphoproteins
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8-Bromo Cyclic Adenosine Monophosphate
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Tetradecanoylphorbol Acetate