Forskolin, a diterpene, exerts its effects by directly stimulating adenylyl cyclase, which catalyzes the conversion of ATP to cAMP, a secondary messenger that activates protein kinase A (PKA). Elevated PKA activity leads to enhanced phosphorylation of target proteins, effectively altering their function. Similarly, IBMX, a methylxanthine derivative, prevents the breakdown of cAMP by inhibiting phosphodiesterases, sustaining an environment conducive to PKA-mediated phosphorylation. The polyphenol compound epigallocatechin gallate and the stilbenoid resveratrol are capable of modulating numerous signaling pathways and affecting various proteins' activity and state of activation.
Ionomycin, a calcium ionophore, and A23187, a carboxylic acid, both serve to increase intracellular levels of calcium, a critical second messenger that activates a suite of calcium-dependent kinases, which then may phosphorylate proteins. Phorbol 12-myristate 13-acetate, a potent activator of protein kinase C (PKC), directly stimulates PKC which is involved in a wide range of cellular functions, including the regulation of protein activities through phosphorylation. Phosphodiesterase inhibitors like sildenafil maintain elevated levels of cAMP and cGMP, thus facilitating the activation of PKA or PKG, kinases that catalyze the transfer of phosphate groups to proteins. LY294002, a flavonoid derivative, acts by inhibiting phosphoinositide 3-kinases (PI3K), thereby affecting downstream signaling cascades, which can lead to modifications in protein activity. The small molecule U0126, known for its inhibitory effect on mitogen-activated protein kinase kinase (MEK), has the capacity to alter the phosphorylation patterns within cells, impacting protein function. Dibutyryl cAMP, a synthetic analog of cAMP, and staurosporine, an alkaloid that inhibits a broad spectrum of kinases, both result in phosphorylation changes that can activate proteins.
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