Chemical activators of ZNF711 utilize a variety of intracellular pathways to promote the protein's activation through phosphorylation, a process where a phosphate group is added to the protein, altering its function. Phorbol 12-myristate 13-acetate (PMA) and 4α-Phorbol are known to activate protein kinase C (PKC), which targets serine and threonine residues on ZNF711 for phosphorylation, resulting in the protein's activation. This is a direct mechanism where PKC, upon activation by these chemicals, catalyzes the transfer of phosphate groups from ATP to ZNF711. Similarly, Forskolin, Dibutyryl-cAMP, and 8-Bromo-cAMP raise the levels of cyclic AMP (cAMP) within the cell, which in turn activates protein kinase A (PKA). PKA then phosphorylates ZNF711, thereby activating it. This cascade is a classic signaling pathway where the elevation of cAMP serves as a second messenger in the activation of PKA, which subsequently phosphorylates target proteins.
Additionally, Ionomycin and Thapsigargin lead to the rise of intracellular calcium levels, triggering the activation of calmodulin-dependent kinases. These kinases can also phosphorylate ZNF711, leading to its activation. Thapsigargin specifically inhibits the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump, causing calcium to accumulate within the cytosol and indirectly promoting the activation of kinases that target ZNF711. On another front, Okadaic Acid and Calyculin A inhibit protein phosphatases PP1 and PP2A, preventing the dephosphorylation of ZNF711, which keeps the protein in an active, phosphorylated state. Anisomycin is another chemical that takes a different route by activating the MAP kinase pathway, which includes ERK among other kinases. These kinases have the capability to phosphorylate ZNF711, leading to its functional activation. Lastly, while Chelerythrine and Bisindolylmaleimide I are typically inhibitors of PKC, they can lead to the activation of alternative kinases that can still phosphorylate ZNF711, highlighting the complex interplay within the cell where blocking one pathway can activate another, resulting in the desired phosphorylation and activation of ZNF711.
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