Forskolin engages the adenylate cyclase enzyme with precision, resulting in an upsurge of cyclic AMP (cAMP), a secondary messenger pivotal in the activation of protein kinase A (PKA). This activation sequence sets the stage for phosphorylation, a post-translational modification essential in the regulation of protein activity. IBMX complements this process by its inhibitory action on phosphodiesterases, enzymes responsible for cAMP degradation, thus augmenting and prolonging the signal initiated by Forskolin.
Genistein's subtle engagement with tyrosine kinases alters phosphorylation landscapes, potentially leading to the activation of a variety of proteins, including those unrelated to its primary inhibitory role. Phorbol esters like PMA specifically activate protein kinase C (PKC), which phosphorylates target proteins, while calcium mobilizers like Ionomycin and Thapsigargin, along with the ionophore A23187, harness the universal second messenger calcium to initiate protein activation through calmodulin-dependent kinases. LY294002 and U0126 selectively inhibit PI3K and MEK respectively, which paradoxically can result in the activation of different proteins due to the complex interplay and compensatory mechanisms inherent in cellular signaling networks. PD98059 and U0126, by targeting MEK, modulate the MAPK/ERK pathway, influencing the activation state of proteins downstream.
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