Tarafdar Anuradha, Michie Alison M
*Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 02D, U.K.
Biochem Soc Trans. 2014 Dec;42(6):1556-62. doi: 10.1042/BST20140255.
The protein kinase C (PKC) family of serine/threonine protein kinases share structural homology, while exhibiting substantial functional diversity. PKC isoforms are ubiquitously expressed in tissues which makes it difficult to define roles for individual isoforms, with complexity compounded by the finding that PKC isoforms can co-operate with or antagonize other PKC family members. A number of studies suggest the involvement of PKC family members in regulating leukaemic cell survival and proliferation. Chronic lymphocytic leukaemia (CLL), the most common leukaemia in the Western world, exhibits dysregulated expression of PKC isoforms, with recent reports indicating that PKCβ and δ play a critical role in B-cell development, due to their ability to link the B-cell receptor (BCR) with downstream signalling pathways. Given the prognostic significance of the BCR in CLL, inhibition of these BCR/PKC-mediated signalling pathways is of therapeutic relevance. The present review discusses the emerging role of PKC isoforms in the pathophysiology of CLL and assesses approaches that have been undertaken to modulate PKC activity.
丝氨酸/苏氨酸蛋白激酶的蛋白激酶C（PKC）家族具有结构同源性，同时表现出显著的功能多样性。PKC亚型在组织中广泛表达，这使得难以确定单个亚型的作用，而且由于发现PKC亚型可以与其他PKC家族成员合作或拮抗，情况变得更加复杂。许多研究表明PKC家族成员参与调节白血病细胞的存活和增殖。慢性淋巴细胞白血病（CLL）是西方世界最常见的白血病，其PKC亚型表达失调，最近的报告表明PKCβ和δ在B细胞发育中起关键作用，因为它们能够将B细胞受体（BCR）与下游信号通路联系起来。鉴于BCR在CLL中的预后意义，抑制这些BCR/PKC介导的信号通路具有治疗相关性。本综述讨论了PKC亚型在CLL病理生理学中的新作用，并评估了调节PKC活性所采用的方法。
