Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
J Biol Chem. 2022 Aug;298(8):102194. doi: 10.1016/j.jbc.2022.102194. Epub 2022 Jun 24.
PKC comprises a large family of serine/threonine kinases that share a requirement for allosteric activation by lipids. While PKC isoforms have significant homology, functional divergence is evident among subfamilies and between individual PKC isoforms within a subfamily. Here, we highlight these differences by comparing the regulation and function of representative PKC isoforms from the conventional (PKCα) and novel (PKCδ) subfamilies. We discuss how unique structural features of PKCα and PKCδ underlie differences in activation and highlight the similar, divergent, and even opposing biological functions of these kinases. We also consider how PKCα and PKCδ can contribute to pathophysiological conditions and discuss challenges to targeting these kinases therapeutically.
蛋白激酶 C 包含一个由丝氨酸/苏氨酸激酶组成的大家族,它们都需要通过脂质的变构激活。虽然蛋白激酶 C 同工型具有显著的同源性,但在亚家族之间以及在亚家族内的各个蛋白激酶 C 同工型之间存在明显的功能分化。在这里,我们通过比较经典(PKCα)和新型(PKCδ)亚家族中具有代表性的蛋白激酶 C 同工型的调节和功能来突出这些差异。我们讨论了 PKCα 和 PKCδ 的独特结构特征如何导致激活的差异,并强调了这些激酶相似、不同甚至相反的生物学功能。我们还考虑了 PKCα 和 PKCδ 如何促成病理生理状况,并讨论了靶向这些激酶治疗的挑战。