IL-1 activation of MAPK pathways. IL-1 binds to its cellular receptor and activates receptor-associated proteins (red), such as IRAK, TRAF6, and TAK1. The result is activation of several MAPK kinases (MKK6, MKK4, MKK7, and MEK1; green), which phosphorylate and active the MAPKs p38, JNK, and ERK (blue). SB203580 inhibits the p38 kinases, while PD98059 blocks activation of MEK1, and as a consequence ERK activation. SP600125 is a novel inhibitor of JNK, described by Han et al. in a recent issue of the JCI (13).