Meller N, Altman A, Isakov N
Department of Microbiology and Immunology, Faculty of Health Sciences, and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
Stem Cells. 1998;16(3):178-92. doi: 10.1002/stem.160178.
Members of the protein kinase C (PKC) family of serine/threonine protein kinases have been implicated in numerous cellular responses in a large variety of cell types. Expression patterns of individual members and differences in their cofactor requirements and potential substrate specificity suggest that each isoenzyme may be involved in specific regulatory processes. The PKCtheta isoenzyme exhibits a relatively restricted expression pattern with high protein levels found predominantly in hematopoietic cells and skeletal muscle. PKCtheta was found to be expressed in T, but not B lymphocytes, and to colocalize with the T-cell antigen receptor (TCR) at the site of contact between the antigen-responding T cell and the antigen-presenting cell (APC). Colocalization of PKCtheta with the TCR was selective for this isoenzyme and occurred only upon antigen-mediated responses leading to T-cell activation and proliferation. PKCtheta was found to be involved in the regulation of transcriptional activation of early-activation genes, predominantly AP-1, and its cellular distribution and activation were found to be regulated by the 14-3-3 protein. Other findings indicated that PKCtheta can associate with the HIV negative factor (Nef) protein, suggesting that altered regulation of PKCtheta by Nef may contribute to the T-cell impairments that are characteristic of infection by HIV. PKCtheta is expressed at relatively high levels in skeletal muscle, where it is suggested to play a role in signal transduction in both the developing and mature neuromuscular junction. In addition, PKCtheta appears to be involved in the insulin-mediated response of intact skeletal muscle, as well as in experimentally induced insulin resistance of skeletal muscle. Further studies suggest that PKCtheta is expressed in endothelial cells and is involved in multiple processes essential for angiogenesis and wound healing, including the regulation of cell cycle progression, formation and maintenance of actin cytoskeleton, and formation of capillary tubes. Here, we review recent progress in the study of PKCtheta and discuss its potential role in various cellular responses.
丝氨酸/苏氨酸蛋白激酶的蛋白激酶C（PKC）家族成员与多种细胞类型中的众多细胞反应有关。各个成员的表达模式及其辅因子需求和潜在底物特异性的差异表明，每种同工酶可能参与特定的调节过程。PKCθ同工酶表现出相对受限的表达模式，高蛋白水平主要在造血细胞和骨骼肌中发现。发现PKCθ在T淋巴细胞而非B淋巴细胞中表达，并与T细胞抗原受体（TCR）在抗原反应性T细胞与抗原呈递细胞（APC）之间的接触部位共定位。PKCθ与TCR的共定位对该同工酶具有选择性，并且仅在导致T细胞活化和增殖的抗原介导反应时发生。发现PKCθ参与早期活化基因（主要是AP-1）转录激活的调节，并且发现其细胞分布和活化受14-3-3蛋白调节。其他研究结果表明，PKCθ可与HIV负因子（Nef）蛋白结合，这表明Nef对PKCθ调节的改变可能导致HIV感染所特有的T细胞损伤。PKCθ在骨骼肌中以相对较高的水平表达，据推测它在发育中和成熟的神经肌肉接头的信号转导中起作用。此外，PKCθ似乎参与完整骨骼肌的胰岛素介导反应以及实验诱导的骨骼肌胰岛素抵抗。进一步的研究表明，PKCθ在内皮细胞中表达，并参与血管生成和伤口愈合所必需的多个过程，包括细胞周期进程的调节、肌动蛋白细胞骨架的形成和维持以及毛细血管的形成。在此，我们综述了PKCθ研究的最新进展，并讨论了其在各种细胞反应中的潜在作用。
