Forskolin, a diterpene, elevate intracellular cyclic AMP (cAMP) concentrations by activating adenylyl cyclase, paving the way for enhanced protein kinase A (PKA) activity. PKA, in turn, can phosphorylate a myriad of proteins, potentially altering their function and regulation. Ionomycin, an ionophore, elevates intracellular calcium levels, which can trigger the activation of calmodulin-dependent kinases, influencing proteins that are sensitive to calcium signaling. Phorbol esters like PMA are potent activators of protein kinase C (PKC), whose members phosphorylate a wide range of substrates, thus modifying their activity. Inhibitors such as SB203580 and U0126 selectively target kinases like p38 MAPK and MEK, respectively. These inhibitors can indirectly affect the activity of proteins by preventing their phosphorylation, thereby altering the signaling pathways in which they participate.
PI3K inhibitors, LY294002 and Wortmannin, demonstrate how the inhibition of upstream signaling molecules can lead to alterations in the activity of downstream proteins. By inhibiting PI3K, these compounds indirectly modulate the PI3K/AKT pathway, a pivotal signaling axis involved in the regulation of numerous proteins. The inhibition of mTOR by Rapamycin exemplifies the significance of key regulatory kinases in controlling protein synthesis and activity. This compound, by inhibiting mTOR, can affect the mTOR signaling pathway, thereby influencing protein activity. Small molecules like 2-APB modulate intracellular calcium release, which, akin to ionomycin, can have a profound effect on proteins associated with calcium signaling.
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