[Frontiers in Bioscience 2, a26-30, September 15, 1997]|
SPERMINE STIMULATES THE PHOSPHORYLATION OF THE NUCLEAR MATRIX PROTEINS CATALYZED BY NUCLEAR KINASE II
Rati Verma and Kuang Yu Chen
Department of Chemistry and The Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08855-0939
Received 8/19/97 Accepted 8/25/97
Nuclear kinase II (nuclear casein kinase 2) is a multifunctional, second messenger-independent protein serine/threonine kinase that phosphorylates many different nuclear proteins, including high mobility group (HMG) proteins, heterogeneous nuclear ribonuleoprotein (hnRNP) fractions, and nuclear matrix proteins, but not histones. The enzyme appears to be essential in growth regulation. However, it is not clear how the enzyme is regulated in vivo. To understand the regulation of this enzyme, we have searched for possible effectors for this enzyme. Spermine, at physiological concentrations, significantly stimlulates nuclear protein phosphorylation catalyzed by nuclear kinase II (NII kinase). Using various subnuclear fractions as substrates, we showed that the stimulatory effect of spermine was confined only to nuclear matrix proteins. Thus, spermine at 1 mM stimulated a >5-fold increase in nuclear matrix phosphorylation, but had little or no effect on the phosphorylation of HMG and hnRNP proteins catalyzed by NII kinase. Similarly, the inhibitory effect of heparin on NII kinase reaction was also substrate-dependent and appeared to be limited to nuclear matrix proteins. Previously, we have shown that spermine inhibits the phosphorylation of the 11,000- and 10,000-dalton nuclear protein catalyzed by NI kinase. Both of these low molecular weight proteins exist in nuclear matrix fraction. Taken together, our data suggest that NI and NII kinase may be regulated by spermine in vivo and that nuclear matrix proteins appear to be the primary target for such a regulation.