MPP4 Activators

Chemical activators of MPP4 play a pivotal role in the modulation of its activity through different signaling pathways. Phorbol 12-myristate 13-acetate (PMA), for instance, directly activates Protein Kinase C (PKC), which can phosphorylate MPP4, enhancing its function in cellular signaling. Similarly, 1-Oleoyl-2-acetyl-sn-glycerol (OAG) mimics diacylglycerol (DAG) to activate PKC isoforms, which also phosphorylates MPP4. Ionomycin and Calcium ionophore A23187 both raise intracellular calcium levels, which can activate calmodulin-dependent protein kinase II (CaMKII). The activation of CaMKII can lead to the phosphorylation of MPP4. Furthermore, forskolin activates adenylyl cyclase, which increases cAMP levels and activates Protein Kinase A (PKA), leading to the phosphorylation and activation of MPP4.

Certain chemicals inhibit the dephosphorylation of MPP4, maintaining it in an active state. Okadaic acid and Calyculin A are inhibitors of protein phosphatases PP1 and PP2A, thus preserving the phosphorylated state of MPP4. Additionally, 8-Bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and N6-Benzoyladenosine 3',5'-cyclic monophosphate (6-Bnz-cAMP) are cAMP analogs that activate PKA, which in turn activates MPP4. Thapsigargin disrupts calcium homeostasis by inhibiting the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), resulting in increased cytosolic calcium levels that can activate kinases such as CaMKII, subsequently leading to MPP4 activation. BIM (Bisindolylmaleimide I), on the other hand, inhibits PKC but can also induce a conformation that leads to basal activity of PKC, resulting in the activation of MPP4.