CALMODULIN CAN MODULATE PROTEIN-PHOSPHORYLATION IN RAT-LIVER CELLS NUCLEI

This report describes the immunological identification of a 60-kDa cal modulin-binding protein, previously detected in the nuclei of rat live r cells (Bachs, O., Lanini, L., Serratosa, J., Coll, M. J., Bastos, R. , Aligue, R., Rius, E., and Carafoli, E. (1990) J. Biol. Chem. 265, 18 595-18600), as the calmodulin-dependent protein phosphatase calcineuri n. Calcineurin could be extracted from the nuclei by incubation with D Nase and RNase, indicating that it is associated with nuclear structur es sensitive to the action of nucleases (chromatin or/and ribonucleopr oteins). The presence of calcineurin in the nuclei of rat liver cells indicates that calmodulin may modulate the phosphorylation level of nu clear proteins by promoting their dephosphorylation. This report also shows that calmodulin inhibits the activity of casein kinase-2 in the nuclear fractions obtained by nuclease extraction. Phosphorylation exp eriments indicate that casein kinase-2 phosphorylates three major subs trates of 100, 42-44, and 37 kDa as well as other minor proteins in th e nuclease extracts. Calmodulin reduces the phosphorylation level of t he two latter major proteins and of a minor band of 50 kDa. Thus, nucl ear calmodulin in rat liver cells could regulate phosphorylation of nu clear proteins by at least two mechanisms: 1) activation of calcineuri n and 2) inhibition of casein kinase-2.