Chemical activators of Pi15 can exert their effects through various pathways, leading to the functional activation of this protein. Calcium chloride, for instance, operates by enhancing calcium-dependent signaling pathways, resulting in the activation of Pi15 through phosphorylation by calcium-activated kinases. Similarly, Ionomycin raises intracellular calcium levels, which triggers downstream kinases to phosphorylate and activate Pi15. Phorbol 12-myristate 13-acetate (PMA) specifically activates protein kinase C (PKC), a kinase that directly targets Pi15 for phosphorylation, leading to its activation. Forskolin, by increasing cAMP levels through the activation of adenylyl cyclase, subsequently activates protein kinase A (PKA), which then targets Pi15 for activation. The cAMP analog Dibutyryl-cyclic AMP (db-cAMP) also activates PKA, setting off a cascade that results in the activation of Pi15.
Further down the list of chemical activators, Okadaic acid and Calyculin A inhibit protein phosphatases, preventing dephosphorylation and thus maintaining Pi15 in an activated state. Anisomycin functions through the activation of stress-activated protein kinases (SAPKs), which subsequently phosphorylate and activate Pi15, integrating it into the cellular stress response. Epidermal Growth Factor (EGF) activates receptor tyrosine kinases, which are part of a signaling cascade effectuating the phosphorylation and activation of Pi15. Phosphatidic acid stimulates the mTOR signaling pathway, known to include kinases that can directly activate Pi15. Spermine can enhance Pi15's structure, promoting its interaction with kinases that activate it through phosphorylation. Lastly, Brefeldin A induces a cellular stress response that activates kinases, which in turn target and activate Pi15, integrating it into a broader cellular adaptation to stress.
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