Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Tissue Barriers. 2021 Jul 3;9(3):1908109. doi: 10.1080/21688370.2021.1908109. Epub 2021 Apr 27.
Claudins (CLDNs) represent major transmembrane proteins of tight junctions and contribute to the barrier function. They also serve as anchors for several signaling proteins, but the underlying molecular basis has yet to be established. The present review covers the recent progress in our understanding of the CLDN signaling pathway in health and disease. We discuss the functional relevance of phosphotyrosine motifs in the C-terminal cytoplasmic domain of CLDNs and define mutual regulation between CLDNs and Src-family kinases (SFKs). In addition, we focus on the crosstalk between CLDN and transcription factor signaling. We also describe how aberrant CLDN-transcription factor signaling promotes or inhibits cancer progression. We propose that a link between various cell adhesion molecules and transcription factors coordinates a range of physiological and pathological events via activation or suppression of target genes.
紧密连接的主要跨膜蛋白为 Claudins（CLDNs），其有助于维持屏障功能。CLDNs 还可作为多种信号蛋白的锚定位点，但其中的潜在分子机制尚未明确。本文综述了在健康和疾病中 CLDN 信号通路的最新研究进展。我们讨论了 CLDN 胞质 C 端尾部磷酸酪氨酸基序的功能相关性，并定义了 CLDN 与 Src 家族激酶（SFKs）之间的相互调控作用。此外，我们还重点关注 CLDN 与转录因子信号之间的串扰。我们还描述了异常的 CLDN-转录因子信号如何促进或抑制癌症进展。我们提出，各种细胞黏附分子和转录因子之间的联系可通过激活或抑制靶基因来协调一系列生理和病理事件。
