NERVE GROWTH-FACTOR ACTIVATES A RAS-DEPENDENT PROTEIN-KINASE THAT STIMULATES C-FOS TRANSCRIPTION PHOSPHORYLATION OF CREB

A mechanism by which the nerve growth factor (NGF) signal is transduce d to the nucleus to induce gene expression has been characterized. An NGF-inducible, Ras-dependent protein kinase has been identified that c atalyzes the phosphorylation of the cyclic AMP response element-bindin g 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 previo usly believed and functions in the nucleus as a general mediator of gr owth factor responses.