PLP-F Activators

Chemical activators of PLP-F can induce its activation via various intracellular signaling pathways by increasing phosphorylation levels on the protein. Forskolin, by directly activating adenylate cyclase, raises cAMP levels within the cell. This spike in cAMP activates protein kinase A (PKA), which then phosphorylates PLP-F, leading to its activation. Similarly, 8-Bromo-cAMP, a cAMP analog, bypasses upstream signaling and directly stimulates PKA, resulting in subsequent phosphorylation and activation of PLP-F. Phorbol 12-myristate 13-acetate (PMA) and 1,2-Dioctanoyl-sn-glycerol (DiC8), synthetic analogs of diacylglycerol, activate protein kinase C (PKC). PKC then targets PLP-F for phosphorylation, culminating in its functional activation.

Additionally, calcium ionophores like ionomycin and A23187 elevate intracellular calcium levels, which in turn activate calcium-dependent kinases such as calmodulin-dependent kinase (CaMK). These kinases can phosphorylate PLP-F, thereby activating it. BAY K8644 exerts its effects by agonizing L-type calcium channels, which also results in increased intracellular calcium and activation of kinases that phosphorylate PLP-F. Thapsigargin contributes to the rise in cytosolic calcium by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pumps, again leading to activation of PLP-F through calcium-dependent phosphorylation. Inhibition of protein phosphatases by compounds like okadaic acid and calyculin A prevents dephosphorylation, thus maintaining PLP-F in a phosphorylated and active state. Anisomycin activates the stress-activated protein kinase (SAPK) pathway, including c-Jun N-terminal kinases (JNKs), which can also specifically target and activate PLP-F through phosphorylation. Conversely, H-89, while primarily a PKA inhibitor, can lead to the compensatory activation of other kinases capable of PLP-F phosphorylation, thereby ensuring its activation through alternative routes.