首页> 外文期刊>American Journal of Physiology >Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal serine 81 phosphorylation site.
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Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal serine 81 phosphorylation site.

机译:蛋白激酶C的激活抑制NH2-末端丝氨酸81磷酸化位点的Cav1.3钙通道。

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摘要

The Ca(v)1.3 (alpha(1D)) variant of L-type Ca(2+) channels plays a vital role in the function of neuroendocrine and cardiovascular systems. In this article, we report on the molecular and functional basis of alpha(1D) Ca(2+) channel modulation by protein kinase C (PKC). Specifically, we show that the serine 81 (S81) phosphorylation site at the NH(2)-terminal region plays a critical role in alpha(1D) Ca(2+) channel modulation by PKC. The introduction of a negatively charged residue at position 81, by converting serine to aspartate, mimicked the PKC phosphorylation effect on alpha(1D) Ca(2+) channel. The modulation of alpha(1D) Ca(2+) channel by PKC was prevented by dialyzing cells with a 35-amino acid peptide mimicking the alpha(1D) NH(2)-terminal region comprising S81. In addition, the data revealed that only betaII- and epsilonPKC isozymes are implicated in this regulation. These novel findings have significant implications in the pathophysiology of alpha(1D) Ca(2+) channel and in the development of PKC isozyme-targeted therapeutics.
机译:L型Ca(2+)通道的Ca(v)1.3(alpha(1D))变体在神经内分泌和心血管系统的功能中起着至关重要的作用。在本文中,我们报告了蛋白激酶C(PKC)的alpha(1D)Ca(2+)通道调节的分子和功能基础。具体来说,我们表明在NH(2)末端区域的丝氨酸81(S81)磷酸化位点在通过PKC的alpha(1D)Ca(2+)通道调制中起关键作用。通过将丝氨酸转化为天冬氨酸,在位置81处引入带负电荷的残基,模仿了alpha(1D)Ca(2+)通道上的PKC磷酸化作用。通过用35个氨基酸的肽模拟包含S81的alpha(1D)NH(2)末端区域透析细胞来防止PKC对alpha(1D)Ca(2+)通道的调节。另外,数据显示仅βII-和εPKC同工酶参与该调控。这些新颖的发现对alpha(1D)Ca(2+)通道的病理生理学和PKC同工酶靶向治疗剂的发展具有重大意义。

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