Membrane localization of cAMP-dependent protein kinase amplifies cAMP signaling to the nucleus in PC12 cells

The A126 cell line, in contrast to its PC12 parent, does not differentiate, accumulate nuclear cAMP-dependent protein kinase A (PKA) catalytic subunit, or transcribe cAMP-dependent promoters in response to cAMP. Total PKA is reduced by 50% and is partly resistant to cAMP-induced dissociation in vivo. Unlike PC12, where PKAII is membrane-associated, PKAII is exclusively cytosolic in A126. Cotransfection with the RII anchor protein (AKAP75) and the PKA catalytic subunit (C-PKA) restored cAMP-induced transcription to levels found in PC12. These data indicate that membrane-bound PKAII amplifies cAMP signaling to the nucleus and suggest that cAMP-mediated responses are specified by the type and cellular localization of the PKA isoform.