NFATc3 activators are a diverse group of chemicals designed to instigate either the direct or indirect activation of the NFATc3 protein. These molecules exploit a multitude of signaling pathways to produce a coherent effect. For instance, Ionomycin and Thapsigargin act by elevating intracellular calcium levels. Elevated calcium ions activate the phosphatase calcineurin, which in turn dephosphorylates NFATc3, allowing it to translocate into the nucleus. Forskolin utilizes a different route; it elevates cAMP levels, leading to an increase in calcineurin activity and subsequent NFATc3 activation. Okadaic Acid preserves NFATc3 in its active form by inhibiting the phosphatases that would otherwise inactivate it.
Some compounds, like Cyclosporine A and Nifedipine, work in a more roundabout manner. Cyclosporine A inhibits proteins that act as calcineurin inhibitors, thus allowing calcineurin to more effectively activate NFATc3. Nifedipine, a calcium channel blocker, causes a homeostatic rise in intracellular calcium, thus indirectly causing NFATc3 activation. Others like Valsartan and Anisomycin work through separate pathways such as the Ang II pathway and the JNK pathway, respectively.
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