Ahmed K, Davis A, Hanten J, Lambert D, McIvor R S, Goueli S A
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.
Cell Mol Biol Res. 1993;39(5):451-62.
Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in the control of cell growth and proliferation. By employing androgen action in the prostate as a model of growth control, we have previously documented that androgens modulate prostatic CK-2 activity in a tissue specific manner. Here we have investigated the role of transcriptional control of prostatic CK-2 in androgenic regulation of its activity. We first cloned and sequenced full length cDNAs encoding the alpha and beta subunits of rat CK-2. The cDNA sequence encoding the alpha subunit corresponded with previously reported sequences for other species, as well as with the derived partial amino acid sequence reported for a rat cDNA. The cloned cDNA for rat CK-2-beta subunit, not reported previously, was also identical in amino acid sequence to that of other species. The cDNAs for alpha and beta subunits were employed as probes to examine the effects of altered androgenic status on transcription of mRNAs for the subunits of prostatic CK-2. Androgen deprivation caused a slow decline in transcription of the a subunit, so that no change was noted at 24 h postcastration; however, at later periods of androgen deprivation a progressive but relatively slow decline was apparent. Administration of a single dose of 5 alpha-dihydrotestosterone (5 alpha-DHT) to 6-d castrated animals did not elicit an early expression of new mRNAs for CK-2-alpha and beta subunits. However, a significant expression of mRNAs for the two subunits was apparent at 8 h (i.e., later stages of the prereplicative phase) reaching a peak in the proliferative phase of prostatic growth (i.e., at 24-48 h) following androgen administration. These data suggest that androgenic regulation of CK-2 gene transcription is not an early event related to androgen action, but is substantial in the prereplicative phase of prostatic cell proliferation mediated by androgen. Further, androgenic stimulation of the mRNA expression for the alpha and beta subunits of CK-2 appears to be differential.
酪蛋白激酶2(CK-2)是一种普遍存在的不依赖信使的蛋白丝氨酸/苏氨酸激酶,与细胞生长和增殖的调控有关。通过将前列腺中的雄激素作用作为生长控制的模型,我们之前已经证明雄激素以组织特异性方式调节前列腺CK-2活性。在此,我们研究了前列腺CK-2转录调控在其活性雄激素调节中的作用。我们首先克隆并测序了编码大鼠CK-2α和β亚基的全长cDNA。编码α亚基的cDNA序列与先前报道的其他物种的序列一致,也与报道的大鼠cDNA推导的部分氨基酸序列一致。之前未报道的大鼠CK-2-β亚基的克隆cDNA在氨基酸序列上也与其他物种相同。α和β亚基的cDNA用作探针,以检查雄激素状态改变对前列腺CK-2亚基mRNA转录的影响。雄激素剥夺导致α亚基转录缓慢下降,因此在去势后24小时未观察到变化;然而,在雄激素剥夺的后期,明显出现渐进但相对缓慢的下降。给6天去势的动物单次注射5α-二氢睾酮(5α-DHT)并未引发CK-2-α和β亚基新mRNA的早期表达。然而,在给药后8小时(即复制前期的后期阶段),两个亚基的mRNA有明显表达,在前列腺生长的增殖期(即24-48小时)达到峰值。这些数据表明,CK-2基因转录的雄激素调节不是与雄激素作用相关的早期事件,而是在雄激素介导的前列腺细胞增殖的复制前期阶段起重要作用。此外,雄激素对CK-2α和β亚基mRNA表达的刺激似乎存在差异。