TMEM120B Activators

Chemical activators of TMEM120B can initiate their effects through several intracellular signaling pathways and interactions. Forskolin, for example, serves as an activator of adenylyl cyclase, leading to an increase in cyclic AMP (cAMP) levels within cells. The elevated cAMP activates protein kinase A (PKA), which then can phosphorylate various proteins. Such phosphorylation events can lead to the activation of TMEM120B as part of downstream signaling cascades. Similarly, Bisindolylmaleimide I, through its inhibitory effect on protein kinase C (PKC), can result in the compensatory activation of alternative pathways that converge on the phosphorylation and subsequent activation of TMEM120B. Increased intracellular calcium is another critical regulator, and compounds like Ionomycin and A23187, both of which increase intracellular calcium levels, can activate calcium-dependent kinases. These kinases may directly or indirectly phosphorylate TMEM120B, resulting in its activation.

Additional routes of activation include the disruption of phosphatase activity, which typically serves to reverse phosphorylation. Okadaic Acid and Calyculin A inhibit phosphatases such as PP1 and PP2A, potentially maintaining TMEM120B in a phosphorylated and active state. Fostriecin, by selectively inhibiting PP2A and PP4, can also maintain or enhance the phosphorylation status of TMEM120B, leading to its activation. Stress-activated protein kinases, which can be activated by Anisomycin, also contribute to the phosphorylation and activation of cellular proteins, including TMEM120B. Synthetic analogs of cAMP, such as Dibutyryl-cAMP and 8-Bromo-cAMP, permeate the cell membrane and activate PKA, further promoting the phosphorylation and activation of TMEM120B through downstream effects. These chemical activators, therefore, utilize diverse cellular mechanisms to ensure the phosphorylation-dependent activation of TMEM120B, highlighting the complex interplay of signaling molecules within the cell.