TMEM190 Activators

TMEM190 can engage various intracellular signaling pathways to initiate its activation. Forskolin is one such activator, directly targeting adenylate cyclase to increase the levels of cyclic AMP (cAMP) within the cell. This rise in cAMP leads to the activation of protein kinase A (PKA), which can phosphorylate TMEM190, thereby altering its activity. Similarly, IBMX works by inhibiting phosphodiesterases, the enzymes responsible for breaking down cAMP, thus sustaining and amplifying the PKA-mediated phosphorylation of TMEM190. Prostaglandin E2 (PGE2) operates through a related mechanism, binding to its G-protein-coupled receptors (GPCRs) and triggering an increase in cAMP, which, in turn, activates PKA and the subsequent phosphorylation of TMEM190.

TMEM190 through calcium-dependent mechanisms. Ionomycin acts as a calcium ionophore, increasing intracellular calcium, which can activate specific calcium-dependent kinases capable of phosphorylating TMEM190. Thapsigargin disrupts calcium homeostasis by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA), again leading to elevated cytosolic calcium levels that may activate kinases targeting TMEM190. A23187, also a calcium ionophore, raises intracellular calcium concentration, potentially facilitating the activation of TMEM190 through calcium-dependent pathways. BAY K8644 further contributes to this elevation by acting as a calcium channel agonist, enhancing calcium influx. This influx of calcium can activate TMEM190 indirectly through the activation of calcium-dependent kinases. Additionally, bradykinin, through its receptor, can activate phospholipase C (PLC), increasing the levels of inositol trisphosphate (IP3) and diacylglycerol (DAG), secondary messengers that also have roles in the regulation of intracellular calcium and the activation of TMEM190. Phorbol 12-myristate 13-acetate (PMA) activates protein kinase C (PKC), which is known to phosphorylate a range of protein targets including TMEM190. Lastly, zinc sulfate can influence TMEM190 activity by modulating the function of kinases and proteins that interact with TMEM190, while ouabain by inhibiting the Na+/K+ ATPase, indirectly affects calcium homeostasis and potentially TMEM190 activity via calcium-dependent signaling pathways.