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  • Furthermore the role of GSK in the pathogenesis of inflammat

    2021-10-23

    Furthermore, the role of GSK-3 in the pathogenesis of inflammation has been widely documented as it accompanies inflammatory conditions such as diabetes mellitus, mood disorders, Alzheimer’s disease, cancer (Jope et al., 2007), and has been associated with atherothrombotic CVD events. However, another interesting finding in this study is that gestational GC exposure in rats decreases GSK-3 which is contrary to our previous finding where nicotine-/or COC-treatment in female rats led to increased GSK-3 accompanied with glucose deregulation and elevated circulating GC. In the same study, decreased GSK-3 was associated with improved gluco-metabolic function (Michael and Olatunji, 2017). Therefore, the finding of the current study suggest that the development of gluco-metabolic dysfunction in this animal model of gestational GC-induced IR is through GSK-3-independent but endoglin-/DPP-4-dependent pathway in female rats.
    Conclusions
    Conflict of interest
    Acknowledgments This research was supported by International Society of Hypertension (ISH) grant for mentors (2017) and Association of African Universities (AAU; 2017).
    Introduction Casein kinase II (CK2) and Glycogen Synthase Kinase-3 (GSK-3) are two ubiquitous, highly expressed serine/threonine kinases that are involved in the regulation of multiple pathways (Pinna, 1994, Woodgett, 1990). Over the last several decades, tremendous advances have been made in understanding the biochemical and biological functions of these proteins in physiological and pathological conditions. Although these studies produced a wealth of knowledge and provided novel insights into a number of physiological processes, there are many unanswered questions regarding the roles of these Caspase-3/7 Inhibitor in health and disease. More recently, the development of inhibitors for these kinases provided the opportunity to modify their activity as a therapeutic strategy for various diseases. Since both CK2 and GSK-3 regulate pathways that are essential for cellular proliferation, it is not surprising that inhibitors of these enzymes were tested first as potential therapeutic agents for malignant diseases. The initial success of these inhibitors in preclinical studies further enhanced interest in the function of CK2 and GSK-3 in regulating cellular proliferation. The recent discovery of a novel CK2-Ikaros signaling axis and its role in the regulation of the phosphatidylinositol 3-kinase (PI3K) pathway in leukemia (Song et al., 2015), along with the known role of GSK-3 in regulating the function of key proteins in PI3K pathway (Al-Khouri et al., 2005, Cordier et al., 2012, Maccario et al., 2007, McCubrey et al., 2015), shed new light on the role of CK2 and GSK-3 in cellular proliferation in leukemia. The purpose of this review is to briefly summarize current knowledge of the function of CK2 and GSK-3, and to highlight several interactions between CK2 and GSK-3-regulated signaling pathways that are relevant for malignant diseases with an emphasis on novel discoveries regarding the role of the CK2-Ikaros axis and GSK-3 in regulating the PI3K pathway in leukemia.
    Casein Kinase II (CK2) Casein Kinase II (CK2) is a ubiquitous serine/threonine-selective pro-oncogenic protein kinase that has become a more prominent target for research due to its effects and key role in tumorigenesis (Gowda et al., 2017a, Pinna, 2002). CK2, a well-conserved, pleiotropic kinase, phosphorylates a variety of substrates that are implicated in gene expression, signal transduction, and other nuclear functions (Meggio and Pinna, 2003). Casein Kinase II was initially identified as an essential protein that phosphorylates casein in vitro in 1954, but it was later shown that casein is not one of its immediate physiological substrates as previously thought (Pinna, 1994). CK2 kinase has a unique structure and is the only protein in the kinase family to have more than three consecutive basic amino acids; interestingly, it has a stretch of six basic amino acids that are responsible for the binding of CK2β (Pinna, 1990).