Smooth muscle protein kinase C.
Smooth muscle protein kinase C.
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平滑肌蛋白激酶C.
DOI：
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发表时间：
1994
影响因子：
2.1
通讯作者：
Kathleen G. Morgan
中科院分区：
文献类型：
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作者：
Michael P. Walsh;J. E. Andrea;Bruce G. Allen;O. Clément‐Chomienne;Elizabeth M. Collins;Kathleen G. Morgan
蛋白激酶 C (PKC) 首次被认为与平滑肌收缩的调节有关，观察到佛波酯会诱导缓慢发展的持续收缩。在某些血管平滑肌中，例如雪貂主动脉，佛波酯诱导的收缩发生时，肌浆游离 Ca2+ 浓度 ([Ca]i) 或肌球蛋白轻链磷酸化不增加。这种反应似乎是由 PKC 的 Ca(2+) 独立同工酶（可能是 PKC epsilon）介导的，因为皂苷通透的单个雪貂主动脉平滑肌细胞（保留受体偶联）在低游离 [Ca2+] (pCa 7.0-8.6) 下对去氧肾上腺素产生反应力，并引发 PKC (PKM) 的组成型活性蛋白水解片段pCa 7 时的收缩与去氧肾上腺素诱导的收缩相当。两种收缩均被 PKC 的伪底物肽抑制剂逆转。这些观察结果表明，α-肾上腺素能激动剂可能在没有 Ca2+ 信号的情况下引发收缩反应：α-肾上腺素能刺激磷脂酰胆碱特异性磷脂酶 C 或 D（后者与磷脂酸磷酸水解酶结合）产生二酰甘油。在[Ca2+]i不增加的情况下，二酰甘油特异性激活所谓的新型PKC，其中ε是已知在血管平滑肌中表达的唯一同工酶。最近的证据表明 PKC 可能引发一系列磷酸化反应，导致丝裂原激活蛋白激酶的激活和细丝相关蛋白 caldesmon 的磷酸化。或者或另外，PKC可以直接磷酸化钙调蛋白，另一种细丝相关蛋白。这些磷酸化预计会减轻这些细丝蛋白对跨桥循环速率的抑制。（摘要截断为 250 字）
Protein kinase C (PKC) was first implicated in the regulation of smooth muscle contraction with the observation that phorbol esters induce slowly developing, sustained contractions. In some vascular smooth muscles, e.g., ferret aorta, phorbol ester induced contractions occur without an increase in sarcoplasmic free-Ca2+ concentration ([Ca]i) or myosin light chain phosphorylation. This response appears to be mediated by a Ca(2+)-independent isoenzyme of PKC (probably PKC epsilon), since saponin-permeabilized single ferret aortic smooth muscle cells, which retain receptor coupling, developed force in response to phenylephrine at low free [Ca2+] (pCa 7.0-8.6) and the constitutively active proteolytic fragment of PKC (PKM) elicited a contraction at pCa 7 comparable with the phenylephrine-induced contraction. Both contractions were reversed by a pseudo-substrate peptide inhibitor of PKC. These observations suggest a mechanism whereby alpha-adrenergic agonists may elicit a contractile response without a Ca2+ signal: alpha-adrenergic stimulation of phosphatidylcholine-specific phospholipase C or D (the latter in conjunction with phosphatidate phosphohydrolase) generates diacylglycerol. In the absence of an increase in [Ca2+]i, diacylglycerol specifically activates so-called novel PKCs, of which epsilon is the only isoenzyme known to be expressed in vascular smooth muscle. Recent evidence suggests that PKC may trigger a cascade of phosphorylation reactions, resulting in activation of mitogen-activated protein kinase and phosphorylation of the thin filament associated protein caldesmon. Alternatively, or additionally, PKC may directly phosphorylate calponin, another thin filament associated protein. These phosphorylations are predicted to alleviate inhibition of the cross-bridge cycling rate by these thin-filament proteins.(ABSTRACT TRUNCATED AT 250 WORDS)