FIGURE 1.

p38^MAPK-MK2 axis is activated in response to diverse inflammatory stimuli. p38^MAPK is a point of convergence for a wide diversity of intracellular signaling pathways triggered by pattern recognition receptors and receptors for cytokines and other inflammatory signaling molecules. Following activation of RAGE, (A) the p38^MAPK-MK2 signaling axis is activated downstream of p21^Ras, via MKK3/6 (Yeh et al., 2001; Ott et al., 2014). Activation of receptors in the IL1R superfamily (B), including the toll-like receptors, signal through MyD88 and IRAK, to phosphorylate TRAF6, which in turn activates MKK3/6 and then p38^MAPK (Martin and Wesche, 2002; Dunne and O’Neill, 2003). (C) Activation of TGFβR, meanwhile leads to activation of p38^MAPK, via TAK1 phosphorylation of MKK3/6 (Yu et al., 2002). This TAK1-dependent pathway is also activated downstream of TNFR1 and TLR3 activation, via RIP1 (Shin et al., 2009). (D) Activation of TNF receptor 1 activates p38^MAPK via TRAF2 phosphorylation of MKK3/6.