Type II protein kinase A up-regulation is sufficient to induce growth inhibition in SK-N-SH human neuroblastoma cells

We have previously reported that overexpression of RII beta subunit of protein kinase A, which markedly reduces RI alpha protein, induces growth inhibition in SK-N-SH human neuroblastoma cells. To determine whether the reduction of RI alpha or protein kinase A isozyme type I is essential in the growth inhibition of SK-N-SH cells, we overexpressed RI alpha in sense and antisense orientation. Type I protein kinase A activity was increased in the RI alpha-overexpressing cells and was decreased in the RI alpha antisense-expressing cells. However, the changes in type I protein kinase A activities did not affect cell growth. Overexpression of RII beta or C alpha increased type II protein kinase A and inhibited cell growth in both cell lines regardless of the type I protein kinase A level. These results indicate that type II protein kinase A is the main effector in the cAMP-mediated growth regulation of SK-N-SH human neuroblastoma cells. (C) 1997 Academic Press.