Dynamics and Membrane Interactions of Protein Kinase C.
Dynamics and Membrane Interactions of Protein Kinase C.
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DOI：
10.1021/acs.biochem.5b00565
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发表时间：
2015-08-18
期刊：
影响因子：
2.9
通讯作者：
Igumenova TI
中科院分区：
文献类型：
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作者：
Igumenova TI
蛋白激酶C （PKC）是一个丝氨酸/苏氨酸激酶家族，通过参与磷酸肌苷信号通路调节多种细胞过程。自从该酶被发现和鉴定为促肿瘤磷酯的第一个受体以来，人们一直致力于了解其结构、功能和调节模式。PKC的激活涉及从胞质自抑制潜伏形式到膜相关活性形式的转变。膜募集步骤伴随着酶的构象重排，这减轻了自抑制相互作用，从而使PKC能够磷酸化其靶标。PKC的多结构域结构和内在的灵活性为这类酶及其与膜相互作用的生物物理和结构生物学研究带来了巨大的挑战和机遇，这是本文的主要焦点。我将重点介绍该领域的最新进展，概述当前的挑战，并确定生物物理学和结构生物学方法可以提供对PKC活性的同工酶特异性调节的见解的领域。
Protein Kinase C (PKC) is a family of Ser/Thr kinases that regulate a multitude of cellular processes through participation in the phosphoinositide signaling pathway. Significant research efforts have been directed at understanding the structure, function, and regulatory modes of the enzyme since its discovery and identification as the first receptor for tumor-promoting phorbol esters. The activation of PKC involves a transition from the cytosolic auto-inhibited latent form to the membrane-associated active form. The membrane recruitment step is accompanied by the conformational rearrangement of the enzyme, which relieves auto-inhibitory interactions and thereby enables PKC to phosphorylate its targets. The multi-domain structure and intrinsic flexibility of PKC present remarkable challenges and opportunities for the biophysical and structural biology studies of this class of enzymes and their interactions with membranes – the major focus of this Current Topics article. I will highlight the recent advances in the field, outline the current challenges, and identify areas where biophysics and structural biology approaches can provide insight into the isoenzyme-specific regulation of PKC activity.