We describe their participation in processes underlying whole-body metabolism and whether alterations in their function might contribute to disease development. In this mini-review, we have summarized the contributions of various scaffold proteins to metabolism and cardiometabolic diseases. Thus, scaffolds have often been underappreciated in the context of metabolism and metabolic diseases. However, little is known whether scaffolds have similar importance in metabolic processes or in the pathogenesis of metabolic diseases, such as diabetes and obesity. For decades, receptors and kinases have been considered to be the key signaling effectors responsible for metabolic processes, such as glucose uptake, lipolysis, and insulin secretion ( 9, 10). Furthermore, they can regulate the enzymatic activity of kinases, such as hormone-sensitive lipase (HSL) ( 8).ĭespite the knowledge that scaffolds are needed to accurately coordinate signaling pathways, it is only within the past 10 years that their roles in metabolism have emerged. For example, scaffolds belonging to the 14-3-3 protein family interact with the phosphorylated form of the transcription factor, FOXO1, leading to it sequestration in the cytoplasm and inhibition of its transcriptional activity ( 7). Scaffolds can bind to one or more signaling effectors to facilitate their spatial or temporal localization within a cell and also regulate the cellular functions of various effectors, including those involved in metabolic signaling pathways ( 4–6). Molecular scaffolds or adaptor proteins (herein referred to as scaffolds) have been proposed to be the principal regulators that ensure such coordination ( 4, 5). Precise coordination of signaling events is necessary to ensure that stimulus-dependent effects are accurately evoked in a particular cell type, and dysregulation of signaling events can lead to the development of diseases, including cancer ( 1–3). Transduction of receptor-mediated signaling pathways requires upstream receptors at the cell membrane and their downstream effector molecules, such as kinases or transcription factors. A thorough understanding of how scaffolds influence metabolism could aid in the discovery of novel therapeutic approaches to treat chronic conditions, such as diabetes, obesity, and cardiovascular disease, for which the incidence of all continue to increase at alarming rates. The aims of the present review were to highlight the importance of scaffold proteins and to raise awareness of their physiological contributions. In the present review, we discuss various scaffold proteins and their involvement in signaling pathways related to metabolism and metabolic diseases. In general, scaffolds are often underappreciated in the context of metabolism or metabolic diseases. However, little is known regarding whether scaffolds have similar roles in the pathogenesis of metabolic diseases. It is well appreciated that changes in the expression or function of signaling effectors, such as receptors or kinases, can influence the development of chronic diseases such as diabetes and obesity. It has only been within the past 10 years that their roles in glucose homeostasis and metabolism have emerged. Among their pleiotropic functions, scaffold proteins are required for the accurate coordination of signaling pathways.
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