MECHANISM OF INTRACELLULAR REGULATION OF PROTEIN-KINASE CK2 - ROLE OFSTIMULUS-MEDIATED SUBNUCLEAR ASSOCIATION

In our studies of protein kinase CK2, or casein kinase 2, we have focu sed on its regulation in relation to altered genomic activity in respo nse to androgen action (through the function of the androgen receptor) in the male accessory sex gland, the prostate. We have documented tha t androgens exert a profound effect on CK2 in the prostate. Investigat ion of androgenic regulation of the molecular expression of prostatic CK2 suggested that CK2 gene transcription, although substantial in the prereplicative phase of cell proliferation, is not an early event in androgen action. The lack of rapid transcriptional regulation of CK2 b y androgens suggested an alternative mechanism for our original observ ations on the early regulation of CK2-mediated reactions. A rigorous a nalysis of the CK2 in different compartments of the prostatic cell has suggested its differential regulation. For example, androgen withdraw al results in a rapid loss of CK2 protein and activity in the prostati c cell nucleus, whereas the activity and protein in the cytosol underg oes a slow decline over several days. A single dose of 5 alpha-dihydro testosterone (5 alpha-DHT) given to 6-d castrated animals results in a n increase in nuclear enzymatic activity as well as immunoreactive CK2 protein within 1 h, while a concomitant decrease is apparent in the c ytosolic fraction. Within the nucleus, there appears to be a different ial androgenic regulation of CK2 such that the enzyme associated with chromatin and nuclear matrix (NM) demonstrates a substantially greater androgen sensitivity than the enzyme in the nucleoplasm. Other experi ments have revealed that a significant part of the nuclear CK2 is asso ciated with the NM, where it is involved in the phosphorylation of sev eral NM proteins. We suggest a growth signal-mediated regulation of CK 2, namely rapid translocation to the nucleus and association with chro matin and NM. Colocalization of CK2 at sites of potential substrates r epresents a mechanism of its intracellular stimulus-mediated functions .