LRRC73 Activators

Chemical activators of LRRC73 initiate a cascade of intracellular events leading to its activation. Calcium ionophore A23187 and Ionomycin both function as catalysts to increase the intracellular calcium concentration. This influx of calcium ions is pivotal for the activation of LRRC73, as it relies on calcium for its functional activity. Similarly, Thapsigargin contributes to the rise in cytosolic calcium by inhibiting the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), which also culminates in the activation of LRRC73 through calcium-dependent mechanisms. Forskolin, on the other hand, employs a different strategy by activating adenylate cyclase, thereby raising the levels of intracellular cAMP. The increase in cAMP levels leads to the activation of cAMP-dependent protein kinase A (PKA), which can phosphorylate LRRC73, thereby activating it.

Additional chemical activators, such as PMA, Epinephrine, and Acetylcholine, modulate LRRC73 through a variety of signaling pathways. PMA activates protein kinase C (PKC), which may directly phosphorylate and activate LRRC73. Epinephrine binds to adrenergic receptors and can lead to an increase in either cAMP or calcium levels, which indirectly triggers PKA or PKC, respectively. These kinases, upon activation, target LRRC73 among other proteins. Acetylcholine engages with muscarinic or nicotinic receptors, which can also lead to an increase in intracellular levels of calcium or cAMP, subsequently activating LRRC73 through similar kinase-mediated pathways. Histamine and Glutamate further contribute to the activation of LRRC73 by binding to their respective receptors, which can result in the release of calcium from intracellular stores or activation of PKC via the DAG pathway. Lastly, chemicals like Hydrogen peroxide and Sodium fluoride modulate the phosphorylation state of LRRC73. While Hydrogen peroxide acts through redox-sensitive pathways, Sodium fluoride inhibits phosphatases leading to an accumulation of phosphorylated proteins, including LRRC73. S-Nitroso-N-acetylpenicillamine (SNAP) releases nitric oxide which increases cGMP levels, thus activating cGMP-dependent protein kinase G (PKG) that may target and phosphorylate LRRC73.