Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB.
A mechanism by which the nerve growth factor (NGF) signal is transduced to the nucleus to induce gene expression has been characterized. An NGF-inducible, Ras-dependent protein kinase has been identified that catalyzes the phosphorylation of the cyclic AMP response element-binding protein (CREB) at Ser-133. Phosphorylation of Ser-133 stimulates the ability of CREB to activate transcription in NGF-treated cells. These findings suggest that CREB has a more widespread function than previously believed and functions in the nucleus as a general mediator of growth factor responses.
Ginty
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DD
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Bonni
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A
Greenberg
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ME
D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D020690:GTPase-Activating Proteins; D016762:Genes, fos / Q000187:drug effects; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D020703:ras GTPase-Activating Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D020690:GTPase-Activating Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D011494:Protein Kinases