TMEM214 Activators

Chemical activators of TMEM214 can initiate a variety of intracellular signaling pathways leading to its phosphorylation and subsequent activation. Phorbol 12-myristate 13-acetate (PMA) operates through the activation of Protein Kinase C (PKC), a family of enzymes known to modify proteins through phosphorylation. When PMA is introduced, PKC is activated and can directly phosphorylate TMEM214. Forskolin, by increasing the intracellular concentration of cAMP, activates PKA which then may target TMEM214 for phosphorylation. Ionomycin, acting as a calcium ionophore, raises the intracellular calcium levels, which can activate a suite of calcium-sensitive kinases capable of phosphorylating TMEM214. Similarly, Thapsigargin leads to increased cytosolic calcium by inhibiting the SERCA pump, subsequently activating calcium-dependent protein kinases that can phosphorylate TMEM214.

Other chemical activators include Okadaic Acid and Calyculin A, both of which inhibit protein phosphatases PP1 and PP2A. This inhibition prevents the dephosphorylation of proteins, maintaining TMEM214 in a phosphorylated state. Anisomycin triggers the activation of stress-activated protein kinases such as JNK and p38 MAPK, which can phosphorylate TMEM214. Hydrogen Peroxide can initiate signaling pathways that include MAPKs, leading to phosphorylation of TMEM214. Sphingosine-1-phosphate, engaging with G protein-coupled receptors, can result in downstream signaling cascades that phosphorylate TMEM214. Epidermal Growth Factor (EGF), through its receptor EGFR, initiates a series of signaling events that activate kinases, which in turn target TMEM214. Lastly, Staurosporine, despite its role as a kinase inhibitor, can lead to the activation of a variety of kinases at certain concentrations, resulting in the phosphorylation of TMEM214, whereas Bisindolylmaleimide I, a specific inhibitor of PKC, may also activate kinases under specific conditions, thus leading to TMEM214 phosphorylation.