Prostatic nuclear cAMP-independent protein kinases (PKs) active towards non-histone proteins (including nuclear matrix proteins) have been established by us to demonstrate early androgenic modulation which may be critical to the initial events in the androgenic control of gene expression in the prostate. We have purified two such nuclear cAMP-independent PKs (N1 and N2). Both of the enzymes phosphorylated phosvitin and casein, but PK-N2 was more active towards non-histone proteins. Similar enzymes in other systems have been implicated in the control of activities related to gene action. We are currently raising antibodies against the two enzymes. For PK-N2, hybridomas generating monoclonal antibodies have been developed. The availability of specific antibodies should facilitate planned studies of cellular regulation and molecular biological control of these PKs in regard to their role in androgen-mediated growth control in the prostate. Relevant to this is our observation that purified prostatic androgen receptor is phosphorylated by one of the androgen-sensitive nuclear PKs. One of our goals has been to examine the nuclear proteins and protein kinases of human prostatic chromatin to identify features which might differ in the neoplastic prostate as compared with the normal. We have completed a study of the general properties of the human normal and benign hypertrophic prostate (BPH) chromatin-associated protein kinase reactions. There was no change in the activity of the BPH chromatin as compared with the normal prostate chromatin when tested with phosvitin or lysine-rich histone as substrate. However, a marked increase (by 150%) was found in PK, the rate of phosphorylation of endogenous chromatin-associated, non-histone proteins in BPH chromatin as compared with the normal. The underlying mechanism of this observation and also similar studies of the chromatin from prostatic carcinoma are in progress. (N)
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