Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases
Program in Molecular Medicine; UMass Metabolic Network
Cardiovascular Diseases | Cellular and Molecular Physiology | Endocrinology | Endocrinology, Diabetes, and Metabolism | Nutritional and Metabolic Diseases
Mitogen-activated kinase kinase kinase kinase 4 (Map4k4), originally identified in small interfering (si)RNA screens and characterized by tissue-specific gene deletions, is emerging as a regulator of glucose homeostasis and cardiovascular health. Recent studies have shown that Map4k4 gene ablation or inhibition of its kinase activity attenuates hyperglycemia and plaque formation in mouse models of insulin resistance and atherosclerosis, and suggest roles for Map4k4 in multiple signaling systems, including NFkappaB activation, small GTPase regulation, the Hippo cascade, and regulation of cell dynamics by FERM domain proteins. This new and promising area of inquiry raises key questions that need to be addressed, such as defining which of the above or other effectors mediate Map4k4 control of metabolic and vascular functions, and identifying upstream activators of Map4k4.
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Citation: Trends Endocrinol Metab. 2016 Jul;27(7):484-92. doi: 10.1016/j.tem.2016.04.006. Epub 2016 May 6. Link to article on publisher's site
Sterile 20 kinases, atherosclerosis, diabetes, insulin resistance
Virbasius, Joseph V. and Czech, Michael P., "Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases" (2016). University of Massachusetts Medical School Faculty Publications. 1055.