蛋白激酶C激活剂对GH3垂体瘤细胞腺苷酸环化酶活性的调节
Regulation of GH3 pituitary tumour-cell adenylate cyclase activity by activators of protein kinase C.
作者信息
Quilliam L A, Dobson P R, Brown B L
机构信息
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, U.K.
出版信息
Biochem J. 1989 Sep 15;262(3):829-34. doi: 10.1042/bj2620829.
The influence of protein kinase C (PKC) activation on cyclic AMP production in GH3 cells has been studied. The stimulation of cyclic AMP accumulation induced by forskolin and cholera toxin was potentiated by 4 beta-phorbol 12,13-dibutyrate (PDBu). Moreover, PDBu, which causes attenuation of the maximal response to vasoactive intestinal polypeptide (VIP), also induced a small right shift in the dose-response curve for VIP-induced cyclic AMP accumulation. PDBu-stimulated cyclic AMP accumulation was unaffected by pretreatment of cells with pertussis toxin or the inhibitory muscarinic agonist, oxotremorine. PDBu stimulation of adenylate cyclase activity required the presence of a cytosolic factor which appeared to translocate to the plasma membrane in response to the phorbol ester. The diacylglycerol-generating agents thyroliberin, bombesin and bacterial phospholipase C each stimulated cyclic AMP accumulation, but, unlike PDBu, did not attenuate the stimulation induced by VIP. These results suggest that PKC affects at least two components of the adenylate cyclase complex. Stimulation of cyclic AMP accumulation is probably due to modification of the catalytic subunit, whereas attenuation of VIP-stimulated cyclic AMP accumulation appears to be due to the phosphorylation of a different site, which may be the VIP receptor.
研究了蛋白激酶C（PKC）激活对GH3细胞中环磷酸腺苷（cAMP）产生的影响。4β-佛波醇12,13-二丁酸酯（PDBu）增强了福斯高林和霍乱毒素诱导的cAMP积累的刺激作用。此外，导致对血管活性肠肽（VIP）最大反应减弱的PDBu，也使VIP诱导的cAMP积累的剂量反应曲线出现小幅右移。PDBu刺激的cAMP积累不受百日咳毒素或抑制性毒蕈碱激动剂氧代震颤素预处理细胞的影响。PDBu对腺苷酸环化酶活性的刺激需要一种胞质因子的存在，该因子似乎会响应佛波酯而转位到质膜。生成二酰基甘油的试剂促甲状腺素释放激素、蛙皮素和细菌磷脂酶C均刺激了cAMP积累，但与PDBu不同的是，它们并未减弱VIP诱导的刺激作用。这些结果表明，PKC至少影响腺苷酸环化酶复合物的两个组分。cAMP积累的刺激可能是由于催化亚基的修饰，而VIP刺激的cAMP积累的减弱似乎是由于不同位点的磷酸化，该位点可能是VIP受体。
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