ACY1L2 Activators

Chemical activators of ACY1L2 can modulate its activity through various signaling pathways, primarily involving the phosphorylation of the protein. Acetylcholine is one such activator that engages with nicotinic or muscarinic receptors, which are linked to G proteins. When these receptors are activated, a cascade of intracellular events unfold, leading to the phosphorylation and subsequent activation of ACY1L2. Similarly, forskolin serves as a direct stimulant of adenylyl cyclase, thereby raising the levels of cAMP within the cell. This increase in cAMP is a signal for protein kinase A (PKA) to phosphorylate ACY1L2, activating it. Bradykinin, through its interaction with B2 receptors, engages phospholipase C, resulting in the generation of diacylglycerol and inositol trisphosphate, which are precursors for the activation of protein kinase C (PKC). PKC can then target ACY1L2 for phosphorylation.

Further into the spectrum of chemical activators, glutamate and histamine both function through their respective G protein-coupled receptors to activate phospholipase C, leading to potential activation of ACY1L2 via kinases. Epinephrine and norepinephrine act on different adrenergic receptors but converge on similar pathways involving either PKA or PKC, which in turn can phosphorylate ACY1L2. Serotonin and dopamine also play their part by binding to their specific G protein-coupled receptors, with serotonin engaging PKC through the 5-HT2 receptors, and dopamine activating PKA via D1-like receptors. Sodium fluoride, an allosteric activator of G proteins, enhances adenylyl cyclase activity, which boosts cAMP levels and activates PKA, leading to the phosphorylation of ACY1L2. Adenosine and angiotensin II round out the list, with adenosine acting through adenosine receptors to potentially increase cAMP and PKA activity, and angiotensin II engaging AT1 receptors to activate phospholipase C, PKC, and ultimately ACY1L2. Each of these chemicals, through their distinct pathways, achieves the common endpoint of ACY1L2 activation.