Chemical activators of ANKRD39 include a variety of compounds that influence intracellular signaling pathways, leading to the phosphorylation and activation of this protein. Forskolin acts directly on adenylate cyclase to increase the production of cyclic AMP (cAMP), a secondary messenger that activates protein kinase A (PKA). Once activated, PKA can phosphorylate ANKRD39, thus modulating its activity. Similarly, Dibutyryl-cAMP (db-cAMP) and 8-Bromo-cAMP, both analogs of cAMP, enter cells and activate PKA, which in turn phosphorylates ANKRD39. Phorbol 12-myristate 13-acetate (PMA) and 4α-Phorbol 12,13-didecanoate are analogs of diacylglycerol (DAG) and activate protein kinase C (PKC). Once PKC is activated, it can phosphorylate ANKRD39. Bisindolylmaleimide I, though primarily an inhibitor of PKC, under certain conditions, can activate certain PKC isoforms, which may then phosphorylate and activate ANKRD39.
Other chemicals activate ANKRD39 through different mechanisms involving calcium signaling and phosphatase inhibition. Ionomycin and A-23187 are calcium ionophores that raise intracellular calcium levels, which can activate calmodulin-dependent kinases capable of phosphorylating ANKRD39. Okadaic Acid and Calyculin A both inhibit protein phosphatases 1 and 2A, which normally dephosphorylate proteins, thereby sustaining ANKRD39 in a phosphorylated state. Anisomycin activates stress-activated protein kinases (SAPKs), which then can also phosphorylate ANKRD39. Lastly, Epigallocatechin gallate (EGCG) influences kinase activity and can enhance the phosphorylation of ANKRD39 through unidentified kinases. Each of these activators, by different means, promotes the phosphorylation and resultant activity of ANKRD39 within cellular signaling pathways.
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