1700042B14Rik Activators

Chemical activators of claudin 34B2 can initiate a cascade of intracellular events that modulate the protein's role in tight junction dynamics. Calcium chloride, by increasing intracellular calcium levels, can activate calmodulin-dependent protein kinases, leading to the phosphorylation of claudin 34B2 and thus enhancing its capacity to maintain tight junction integrity. Similarly, thapsigargin, by inhibiting the SERCA pump, causes a surge in cytosolic calcium which then activates kinases that phosphorylate claudin 34B2. Ionomycin also raises intracellular calcium, using a different mechanism as a calcium ionophore, but ultimately resulting in the activation of the same calcium-dependent pathways that phosphorylate and activate claudin 34B2. Histamine triggers an influx of calcium by binding to its receptors, and hydrogen peroxide, acting as a signaling molecule, may influence kinases that phosphorylate claudin 34B2, thereby participating in the modulation of tight junctions. Zinc chloride has a similar effect but operates by modulating the activity of kinases and phosphatases that can phosphorylate claudin 34B2.

In parallel, ATP, through its action on purinergic receptors, and Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), both result in the phosphorylation of claudin 34B2. Forskolin raises cAMP levels, which then activate PKA, and this kinase similarly targets claudin 34B2 for phosphorylation. 1,2-Dioctanoyl-sn-glycerol (DiC8), a DAG analog, activates PKC, which also leads to the phosphorylation and activation of claudin 34B2. The cyclic nucleotides, cGMP and the nitric oxide donor S-Nitroso-N-acetylpenicillamine, via PKG, can mediate the phosphorylation events that activate claudin 34B2. Collectively, these chemical activators utilize different pathways to converge on the phosphorylation and activation of claudin 34B2, thereby influencing tight junction composition and function.