Herring B Paul, El-Mounayri Omar, Gallagher Patricia J, Yin Feng, Zhou Jiliang
Dept. of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA.
Am J Physiol Cell Physiol. 2006 Nov;291(5):C817-27. doi: 10.1152/ajpcell.00198.2006. Epub 2006 Jun 14.
The mylk1 gene is a large gene spanning approximately 250 kb and comprising at least 31 exons. The mylk1 gene encodes at least four protein products: two isoforms of the 220-kDa myosin light chain kinase (MLCK), a 130-kDa MLCK, and telokin. Transcripts encoding these products are derived from four independent promoters within the mylk1 gene. The kinases expressed from the mylk1 gene have been extensively characterized and function to regulate the activity of nonmuscle and smooth muscle myosin II. Activation of these myosin motors by MLCK modulates a variety of contractile processes, including smooth muscle contraction, cell adhesion, migration, and proliferation. Dysregulation of these processes contributes to a number of diseases. The noncatalytic gene product telokin also has been shown to modulate contraction in smooth muscle cells through its ability to inhibit myosin light chain phosphatase. Given the crucial role of the products of the mylk1 gene in regulating numerous contractile processes, it seems intuitive that alterations in the transcriptional activity of the mylk1 gene also will have a significant impact on many physiological and pathological processes. In this review we highlight some of the recent studies that have described the transcriptional regulation of mylk1 gene products in smooth muscle tissues and discuss the implications of these findings for regulation of expression of other smooth muscle-specific genes.
mylk1基因是一个大基因,跨度约250 kb,至少包含31个外显子。mylk1基因编码至少四种蛋白质产物:220 kDa肌球蛋白轻链激酶(MLCK)的两种同工型、一种130 kDa的MLCK和端激酶。编码这些产物的转录本源自mylk1基因内的四个独立启动子。mylk1基因表达的激酶已得到广泛表征,其功能是调节非肌肉和平滑肌肌球蛋白II的活性。MLCK对这些肌球蛋白马达的激活调节了多种收缩过程,包括平滑肌收缩、细胞黏附、迁移和增殖。这些过程的失调会导致多种疾病。非催化基因产物端激酶也已被证明能够通过抑制肌球蛋白轻链磷酸酶来调节平滑肌细胞的收缩。鉴于mylk1基因产物在调节众多收缩过程中的关键作用,mylk1基因转录活性的改变也会对许多生理和病理过程产生重大影响,这似乎是不言而喻的。在这篇综述中,我们重点介绍了一些最近描述平滑肌组织中mylk1基因产物转录调控的研究,并讨论了这些发现对其他平滑肌特异性基因表达调控的意义。