Kawabe J, Iwami G, Ebina T, Ohno S, Katada T, Ueda Y, Homcy C J, Ishikawa Y
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
J Biol Chem. 1994 Jun 17;269(24):16554-8.
Cyclic AMP production within cells is altered upon protein kinase C (PKC) activation; however, whether PKC directly modulates adenylyl cyclase (AC) catalytic activity has been controversial. Molecular studies have elucidated the existence of multiple PKC isoenzymes although the functional role of this diversity is not clear. Using purified PKC and AC isoenzymes, we demonstrate that PKC zeta directly phosphorylates type VAC, leading to an approximate 20-fold increase in its catalytic activity, a significantly larger enhancement than that achieved with forskolin (approximately 5-fold), the most potent activator of AC. When forskolin and PKC phosphorylation are combined, type V AC catalytic activity is increased 100-fold over basal levels. The two PKC isoenzymes (alpha and zeta) are additive in their capacity to activate AC, although PKC alpha is less potent than PKC zeta. Our data indicate that PKC can directly and potently regulate AC activity in an isoenzyme-specific manner, suggesting that direct cross-talk plays a major role in coordinating the activity of these two principal signal transduction pathways.
细胞内的环磷酸腺苷（cAMP）产量在蛋白激酶C（PKC）激活后会发生改变；然而，PKC是否直接调节腺苷酸环化酶（AC）的催化活性一直存在争议。分子研究已阐明多种PKC同工酶的存在，尽管这种多样性的功能作用尚不清楚。我们使用纯化的PKC和AC同工酶证明，PKC ζ直接磷酸化V型AC，导致其催化活性增加约20倍，这一增强幅度明显大于AC最有效的激活剂福斯可林所实现的增强幅度（约5倍）。当福斯可林和PKC磷酸化联合使用时，V型AC催化活性比基础水平增加100倍。两种PKC同工酶（α和ζ）在激活AC的能力上具有累加性，尽管PKC α的效力低于PKC ζ。我们的数据表明，PKC可以以同工酶特异性的方式直接且有力地调节AC活性，这表明直接的相互作用在协调这两条主要信号转导途径的活性中起主要作用。
