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.
Kim
S N
SN
Department of Molecular Biology, Seoul National University, Republic of Korea.
Lee
G R
GR
Hwang
E S
ES
Lee
J H
JH
Park
S D
SD
Cho-Chung
Y S
YS
Hong
S H
SH
D000345:Affinity Labels; D015152:Blotting, Northern; D015153:Blotting, Western; D002384:Catalysis; D002455:Cell Division / Q000187:drug effects; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics; D016376:Oligonucleotides, Antisense; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000345:Affinity Labels; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D006131:Growth Inhibitors; D016376:Oligonucleotides, Antisense; C517834:PRKAR1A protein, human; C517837:PRKAR2B protein, human; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases