Besides phosphorylating and subsequently degrading the molecules that inhibit NF-κB, protein kinases can also target the functional domains of NF-κB proteins themselves to optimally activate NF-κB. NF-κB proteins can be phosphorylated in the cytoplasm or nucleus by such kinases as glycogen synthase kinase 3β (GSK3β) [49], TRAF-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) [50, 51], PKAc [20], mitogen- and stress-activated protein kinase-1 (MSK-1) [52], MAP3K NIK[53], Tpl2, PKC-θ [54], PI3K, Akt [55–57], p38 MAPK [58], protein tyrosine kinase, PKC-δ [59], RHO-kinase 2 [60], Mitogen activated protein kinase kinase 3 (MEKK3) [61], and receptor tyrosine kinases such as epidermal growth factor receptor, human epidermal growth factor receptor 2 [62]. Antagonistic antibodies or kinase inhibitors that target these molecules may decrease NF-κB activation. Some kinase inhibitors that have the potential to inhibit NF-κB activation include SB203580 and PD0980589 (MAPK inhibitors) [58]; denbinobin (TAK1 inhibitor) [63]; tyrosine kinase inhibitors [62]; rhein, (an MEKK inhibitor) [64, 65]; TNAP, betaine (NIK inhibitors) [66–68], epoxyquinol B (a TAK1 crosslinker) [69]; M2L (an extracellular signal-regulated kinase 2 inhibitor) [70, 71]; CCK-8 (a p38 kinase kinase inhibitor) [72], KSR2 (an MEKK3 inhibitor) [73], golli BG21 (a PKC inhibitor) [74].
