STIM2 activators represent a class of chemical compounds that indirectly influence the activity of the Stromal Interaction Molecule 2 (STIM2) protein through their effects on calcium signaling and homeostasis within cells. STIM2 plays a pivotal role in cellular calcium regulation by sensing changes in intracellular calcium levels and initiating downstream signaling events. The identified chemicals within this class act by modulating calcium dynamics, primarily affecting the calcium stores within the endoplasmic reticulum (ER). Thapsigargin, for instance, is an established STIM2 activator that inhibits the SERCA pump, responsible for transporting calcium back into the ER. This inhibition results in calcium depletion within the ER, which STIM2 senses, leading to its activation. Similarly, compounds like caffeine and ionomycin release calcium from intracellular stores, including the ER, indirectly activating STIM2 by reducing ER calcium levels.
Ryanodine receptor agonists, such as ryanodine, release calcium from intracellular stores, potentially influencing STIM2 through changes in ER calcium concentration. Calcium channel blockers like verapamil and nifedipine modulate calcium fluxes, potentially affecting STIM2 indirectly by altering calcium dynamics. These chemicals share a common theme of influencing calcium signaling, which is intricately linked to STIM2 activity. By impacting calcium stores, transport, or fluxes, they can indirectly trigger STIM2 activation and its role in mediating calcium-dependent cellular processes.
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