highlighted topics Signal Transduction in Smooth Muscle Invited Review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression
highlighted topics Signal Transduction in Smooth Muscle Invited Review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression
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特邀评论：平滑肌中 cGMP 依赖性蛋白激酶信号传导机制：从音调调节到基因表达。 J Appl Physiol 91: 1421–1430, 2001.—cGMP 是通过与细胞内受体蛋白相互作用产生作用的第二信使。在平滑肌细胞中，cGMP 的主要受体之一是丝氨酸/苏氨酸蛋白激酶，即 cGMP 依赖性蛋白激酶 (PKG)。 PKG 已被证明可以催化许多生理相关蛋白质的磷酸化，其功能是调节平滑肌细胞的收缩活动。这些包括调节细胞内游离钙水平、细胞骨架和平滑肌肌球蛋白调节轻链磷酸化状态的蛋白质。其他研究表明，体外培养的血管平滑肌细胞 (VSMC) 可能会停止表达 PKG，并且会巧合地获得非收缩性合成表型。 PKG 表达恢复为合成表型 VSMC 导致细胞获得更具收缩性的表型。这些最近的研究表明 PKG 控制 VSMC 基因表达，进而调节细胞的表型调节。因此，PKG 基因表达的调节似乎与 VSMC 的表型调节有关。由于多种血管疾病与血管壁中合成的纤维增殖性 VSMC 的积累有关，因此一氧化氮/cGMP/PKG 通路活性的变化可能与这些疾病的发生有关。 Ca 2 1 通过L 型Ca 2 1 通道流入。 Ca 2 1 流入减少的净效应是整体细胞 Ca 2 1 和松弛的减少。 PKG 还可能具有抑制 Ca 2 1 通道活性的直接作用。
Invited Review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 91: 1421–1430, 2001.—cGMP is a second messenger that produces its effects by interacting with intracellular receptor proteins. In smooth muscle cells, one of the major receptors for cGMP is the serine/ threonine protein kinase, cGMP-dependent protein kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of physio-logically relevant proteins whose function it is to regulate the contractile activity of the smooth muscle cell. These include proteins that regulate free intracellular calcium levels, the cytoskeleton, and the phosphoryla- tion state of the regulatory light chain of smooth muscle myosin. Other studies have shown that vascular smooth muscle cells (VSMCs) that are cultured in vitro may cease to express PKG and will, coincidentally, acquire a noncontractile, synthetic phenotype. The restoration of PKG expression to the synthetic phenotype VSMC results in the cells acquir-ing a more contractile phenotype. These more recent studies suggest that PKG controls VSMC gene expression that, in turn, regulates phenotypic modulation of the cells. Therefore, the regulation of PKG gene expression appears to be linked to phenotypic modulation of VSMC. Because several vascular disorders are related to the accumulation of synthetic, fibropro- liferative VSMC in the vessel wall, it is likely that changes in the activity of the nitric oxide/cGMP/PKG pathway is involved the development of these diseases. in Ca 2 1 influx through L-type Ca 2 1 channels. The net effect of decreased Ca 2 1 influx would be a decrease in global cell Ca 2 1 and relaxation. PKG may also have direct effects to inhibit Ca 2 1 channel activity.