Slater Simon J, Ho Cojen, Stubbs Christopher D
Department of Anatomy, Pathology and Cell Biology, Thomas Jefferson University, Room 271 JAH, 1020 Locust St., Philadelphia, PA 19107, USA.
Chem Phys Lipids. 2002 Jun;116(1-2):75-91. doi: 10.1016/s0009-3084(02)00021-x.
The family of protein kinase C (PKC) isozymes belongs to a growing class of proteins that become active by associating with membranes containing anionic phospholipids, such as phosphatidylserine. Depending on the particular PKC isoform, this process is mediated by Ca(2+)-binding to a C2 domain and interaction of activators such as 1,2-diacyl-sn-glycerol or phorbol esters with tandem C1 domains. This cooperation between the C1 and C2 domains in inducing the association of PKC with lipid membranes provides the energy for a conformational change that consists of the release of a pseudosubstrate sequence from the active site, culminating in activation. Thus, the properties of the interactions of the C1 and C2 domains with membranes, both as isolated domains, and as modules in the full length PKC isoforms, have been the subject of intense scrutiny. Here, we review the findings of studies in which fluorescent phorbol esters have been utilized to probe the properties of the C1 domains of PKC with respect to the interaction with activators, the subsequent interaction with membranes, and the role of the activating conformational change that leads to activation.
蛋白激酶C（PKC）同工酶家族属于一类不断增多的蛋白质，这类蛋白质通过与含有阴离子磷脂（如磷脂酰丝氨酸）的膜结合而变得活跃。根据特定的PKC同工型，这一过程由钙离子结合到C2结构域以及激活剂（如1,2 - 二酰基 - sn - 甘油或佛波酯）与串联的C1结构域相互作用介导。C1和C2结构域在诱导PKC与脂质膜结合方面的这种协同作用为构象变化提供了能量，该构象变化包括从活性位点释放假底物序列，最终导致激活。因此，C1和C2结构域与膜相互作用的特性，无论是作为分离的结构域，还是作为全长PKC同工型中的模块，都一直是深入研究的对象。在这里，我们回顾了利用荧光佛波酯来探究PKC的C1结构域在与激活剂相互作用、随后与膜相互作用以及导致激活的激活构象变化的作用方面的研究结果。
