Protein Kinase C and Apoptosis
Protein Kinase C and Apoptosis
复制标题
DOI：
10.1007/978-1-59745-199-4_2
复制
发表时间：
2007-11
期刊：
影响因子：
--
通讯作者：
M. Reyland
中科院分区：
文献类型：
--
作者：
M. Reyland
蛋白激酶C(PKC)家族由十个结构上相关的丝氨酸/苏氨酸蛋白激酶组成。PKC亚型是细胞增殖和存活的关键调节因子，其表达或活性在某些人类疾病中会发生改变，尤其是癌症。PKC异构体特异性工具的开发和利用，包括显性抑制激酶、特定PKC异构体被破坏的小鼠模型，以及PKC异构体特异性反义/siRNA的开发和利用，使得研究能够确定PKC在细胞凋亡途径中的异构体特异性功能。从这些途径可以看出，传统的亚型，特别是PKα和PKCβ，以及非典型的PKC，PKCPKCι/λKζ似乎是抗凋亡/促生存的。新的异构体PKCδ主要是促凋亡的，而在大多数研究中，PKCε似乎抑制了细胞的凋亡。对促凋亡和抗凋亡亚型的鉴定表明，PKC亚型可能作为分子传感器发挥作用，在有利的条件下促进细胞存活，并在需要时执行异常或受损细胞的死亡。本章讨论了目前已知的特定亚型对细胞凋亡的贡献，以及PKC信号转导如何与其他分子调节因子结合促进或抑制细胞凋亡。
The protein kinase C (PKC) family consists of ten structurally related serine/threonine protein kinases. PKC isoforms are critical regulators of cell proliferation and survival and their expression or activity is altered in some human diseases, particularly cancer. The development and utilization of PKC isoform specific tools, including dominant inhibitory kinases, mouse models in which specific PKC isoforms have been disrupted, and PKC isoform specific antisense/siRNA, has allowed studies to define isoform-specific functions of PKC in the apoptotic pathway. From these approaches a pattern is emerging in which the conventional isoforms, particularly PKα and PKCβ and the atypical PKCs, PKCPKCι/λ Kζ appear to be anti-apoptotic/pro-survival. The novel isoform, PKCδ is primarily pro-apoptotic, whereas PKCε in most studies appears to suppress apoptosis. The identification of both pro- and anti-apoptotic isoforms suggests that PKC isoforms may function as molecular sensors, promoting cell survival under favorable conditions, and executing the death of abnormal or damaged cells when needed.This chapter discusses what is currently known about the contribution of specific isoforms to apoptosis, and how signal transduction by PKC integrates with other molecular regulators to promote or inhibit apoptosis.