V-ATPase G3 Activators

V-ATPase G3 Activators, such as Forskolin, IBMX, and 8-Br-cAMP, function through the activation of adenylate cyclase, which increases the levels of intracellular cAMP. These increased cAMP levels in turn activate Protein Kinase A (PKA), which phosphorylates and activates ATP6V1G3, enhancing V-ATPase activity. Some activators, including Bafilomycin A1 and Concanamycin A, function by inhibiting V-ATPase, which leads to an accumulation of protons in the cytosol. This triggers a compensatory response that includes the activation of ATP6V1G3.

Another group of activators, such as LY294002 and Rottlerin, act through the inhibition of other pathways, which leads to an upregulation of PKA activity and subsequent phosphorylation and activation of ATP6V1G3. In contrast, Okadaic acid and Calyculin A function by inhibiting protein phosphatases, such as PP1 and PP2A, which prevents the dephosphorylation of ATP6V1G3, maintaining its active state. Lastly, activators such as FTY720 and Zardaverine function by increasing cAMP levels through different mechanisms, leading to the activation of PKA and subsequent phosphorylation and activation of ATP6V1G3.