Mechanism of intracellular regulation of protein kinase CK2: Role of stimulus-mediated subnuclear association

In our studies of protein kinase CK2, or casein kinase 2, we have focused on its regulation in relation to altered genomic activity in response to androgen action (through the function of the androgen receptor) in the male accessory sex gland, the prostate. We have documented that androgens exert a profound effect on CK2 in the prostate. Investigation 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 by androgens suggested an alternative mechanism for our original observations on the early regulation of CK2-mediated reactions. A rigorous analysis of the CK2 in different compartments of the prostatic cell has suggested its differential regulation. For example, androgen withdrawal results in a rapid loss of CK2 protein and activity in the prostatic cell nucleus, whereas the activity and protein in the cytosol undergoes a slow decline over several days. A single dose of 5α-dihydrotestosterone (5α-DHT) given to 6d castrated animals results in an increase in nuclear enzymatic activity as well as immunoreactive CK2 protein within 1 h, while a concomitant decrease is apparent in the cytosolic fraction. Within the nucleus, there appears to be a differential 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 experiments have revealed that a significant part of the nuclear CK2 is associated with the NM, where it is involved in the phosphorylation of several NM proteins. We suggest a growth signal-mediated regulation of CK2, namely rapid translocation to the nucleus and association with chromatin and NM. Colocalization of CK2 at sites of potential substrates represents a mechanism of its intracellular stimulus-mediated functions.