Wood J P, McCord R J, Osborne N N
Nuffield Laboratory of Ophthalmology, University of Oxford, U.K.
Neurochem Int. 1997 Feb;30(2):119-36. doi: 10.1016/s0197-0186(96)00049-6.
The protein kinase C (PKC) family of serine/threonine kinase isoenzymes are universally expressed in vertebrate tissues where they control vital cellular functioning. PKC comprises twelve currently identified mammalian isoenzymes, described in three distinct groups according to their need for different effector stimulation. Immunological localisation studies in various vertebrate retinas have indicated the presence, so far, of eight of the PKC subspecies, each with a unique cellular distribution in this tissue. Use of these immunological probing techniques with antibodies raised to the individual PKC family members by immunohistochemistry and western blotting, along with biochemical tools such as the potent activators, the tumour-promoting phorbol esters can hopefully lead to elucidation of the roles of these enzymes in the neural retina. Research work to date has pinpointed a number of roles for PKC in this tissue including control of dopamine release, modulation of glutamate receptor function (probably by a process of direct receptor phosphorylation), phosphorylatory modulation of GABAC-receptor function, an involvement in the retinal ischaemic cascade process (the relevance of which is unknown as yet), involvement in control of cytoskeletal interactions by cytoskeletal element-kinase action and feedback control of enzymes involved in the process of inositol phosphate signalling. PKC has been shown to have an important regulatory role in the process of phototransduction: many of the enzymes and proteins making up the phototransduction cascade act as in vitro and in vivo substrates for PKC-dependent phosphorylation and can have their normal function modified in this way. Also, PKC has been implicated in the control of spinule formation in the retina, a process involved in retinal synaptic plasticity and functioning. All of this work has been described, herein. Collation and utilisation of knowledge of all of the work described here may help us to determine the exact roles for individual isoenzymes in the retina. This in turn may help us to understand and further to prevent pathological conditions leading to inappropriate retinal functioning and possible blindness. Furthermore, understanding the roles of PKC in the neural retina may lead us to vital clues in the understanding of the functioning of this important group of enzymes in the nervous system as a whole and eventually to the prevention of many major neuropathological disorders.
丝氨酸/苏氨酸激酶同工酶的蛋白激酶C（PKC）家族在脊椎动物组织中普遍表达，在这些组织中它们控制着重要的细胞功能。PKC目前包括12种已鉴定的哺乳动物同工酶，根据它们对不同效应器刺激的需求分为三个不同的组。对各种脊椎动物视网膜的免疫定位研究表明，到目前为止，PKC的八个亚类存在于该组织中，每个亚类在该组织中都有独特的细胞分布。通过免疫组织化学和蛋白质印迹法，使用针对单个PKC家族成员产生的抗体的这些免疫探测技术，以及诸如强效激活剂、促肿瘤佛波酯等生化工具，有望阐明这些酶在神经视网膜中的作用。迄今为止的研究工作已经确定了PKC在该组织中的许多作用，包括控制多巴胺释放、调节谷氨酸受体功能（可能通过直接受体磷酸化过程）、对GABAC受体功能的磷酸化调节、参与视网膜缺血级联过程（其相关性目前尚不清楚）、通过细胞骨架元件激酶作用参与控制细胞骨架相互作用以及对参与肌醇磷酸信号传导过程的酶的反馈控制。PKC已被证明在光转导过程中具有重要调节作用：构成光转导级联反应的许多酶和蛋白质作为PKC依赖性磷酸化的体外和体内底物，并且其正常功能可以通过这种方式被改变。此外，PKC还与视网膜中棘状突起的形成控制有关，这一过程涉及视网膜突触可塑性和功能。本文已描述了所有这些工作。整理和利用此处描述的所有工作的知识可能有助于我们确定单个同工酶在视网膜中的具体作用。这反过来可能有助于我们理解并进一步预防导致视网膜功能异常和可能失明的病理状况。此外，了解PKC在神经视网膜中的作用可能会为我们理解这一重要酶类在整个神经系统中的功能提供重要线索，并最终预防许多主要的神经病理疾病。
