Membrane-bound cAMP-dependent protein kinase controls cAMP-induced differentiation in PC12 cells

The A126 cell line, a derivative of PC12, is defective in cAMP-induced tran scription and does not differentiate in the presence of cAMP. In these cell s overexpression of a cAMP-dependent protein kinase (PKA) anchor protein, A KAP75, and of the PKA catalytic subunit substantially increased the fractio n of PKAIII bound to the membrane, stimulated the transcription of cAMP-ind uced genes, and induced terminal differentiation. Conversely, wild type PC1 2 cells expressing a derivative of the AKAP75 protein, AKAP45, which binds the PKA regulatory subunits RII, but fails to locate them to the membranes, induced translocation of PKAII to the cytosol, These cells did not efficie ntly accumulate PRA catalytic subunit in the nuclei when stimulated with CA MP, did not transcribe cAMP-induced genes, and failed to differentiate when exposed to cAMP. These data indicate that membrane-bound PKA positively co ntrols the transcription of cAMP-induced genes and differentiation in PC12 cells.