Bcl-7a Activators

Chemical activators of Bcl-7a initiate a cascade of intracellular events leading to its phosphorylation and subsequent activation. Phorbol 12-myristate 13-acetate (PMA) engages this process by activating protein kinase C (PKC), which directly phosphorylates Bcl-7a. Similarly, diacylglycerol (DAG), a natural activator of PKC, and bryostatin 1, a modulator of PKC, can also promote the activation of Bcl-7a through PKC-mediated phosphorylation. Phosphatidic acid, another lipid second messenger, activates PKC, potentially leading to the phosphorylation of Bcl-7a. Forskolin, by elevating intracellular cAMP levels, activates protein kinase A (PKA) which can then target Bcl-7a. Ionomycin and A23187, both calcium ionophores, raise intracellular calcium levels, which activate calcium-dependent PKC isoforms, thereby facilitating the phosphorylation and activation of Bcl-7a.

In contrast, okadaic acid and calyculin A, inhibitors of protein phosphatases 1 and 2A, prevent the dephosphorylation of proteins, indirectly maintaining Bcl-7a in a phosphorylated state. Thapsigargin, by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA), increases cytosolic calcium concentration, which can activate calcium-dependent kinases that phosphorylate Bcl-7a. FTY720, after being phosphorylated to form FTY720-P, acts on sphingosine-1-phosphate receptors, which can initiate signaling pathways leading to the activation of kinases that phosphorylate Bcl-7a. Anisomycin, while primarily known as a protein synthesis inhibitor, can activate stress-activated protein kinases (SAPKs) like JNK, which may then target Bcl-7a for phosphorylation, resulting in its activation. Each of these chemicals, through their distinct mechanisms, ensures the phosphorylation and activation of Bcl-7a, thereby influencing its role in cellular signaling pathways.