TMEM179B Activators

TMEM179B function via diverse intracellular signaling pathways to modulate its activity. Forskolin, a diterpene, directly stimulates adenylyl cyclase, which in turn elevates intracellular cAMP levels. The increased cAMP activates protein kinase A (PKA), which can phosphorylate TMEM179B, leading to its activation. Similarly, IBMX, by inhibiting phosphodiesterases, prevents the breakdown of cAMP and cGMP, thus sustaining their levels in the cell and enhancing PKA or PKG activity, which can also target TMEM179B for phosphorylation. Isoproterenol, a beta-adrenergic agonist, and PGE2, through its action on G-protein-coupled EP receptors, both result in increased cAMP production via adenylyl cyclase activation. This rise in cAMP further triggers PKA and may influence the phosphorylation state of TMEM179B. Rolipram, by selectively inhibiting phosphodiesterase-4, and Dibutyryl-cAMP, a permeable analog of cAMP, both elevate cAMP levels and thereby activate PKA, which can subsequently phosphorylate TMEM179B.

Continuing the activation cascade, ionomycin and A23187 act as calcium ionophores, increasing intracellular calcium concentrations. The influx of calcium ions can activate calcium/calmodulin-dependent kinases (CaMK), which may then phosphorylate TMEM179B. Phorbol 12-myristate 13-acetate (PMA) activates protein kinase C (PKC), a kinase that can phosphorylate various substrates including TMEM179B. BAY 60-6583, an adenosine receptor agonist, increases cAMP, which is a signal for PKA activation that can lead to the phosphorylation of TMEM179B. Zaprinast inhibits phosphodiesterases 5 and 6, increasing cGMP levels, which in turn can activate PKG, another kinase with the capacity to phosphorylate TMEM179B. Anisomycin, while not directly influencing cAMP or calcium pathways, activates stress-activated protein kinases such as JNK, which can also target TMEM179B for activation through phosphorylation. These chemicals, through their varied mechanisms, engage different kinases that converge on the phosphorylation and regulation of TMEM179B activity.