Regulation of myosin light chain kinase and telokin expression in smooth muscle tissues

Abstract

The mylk1 gene is a large gene spanning ∼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.