Activation of mitogen-activated protein kinase (MAPK; shown in yellow) pathways by IL-1. Stimulation by IL-1 activates the MAPK kinase kinases (MAPKKKs; shown in blue), transforming-growth-factor-β-activated kinase-1 (TAK 1) and Raf, which then phosphorylate and activate several MAPK kinases (MAPKKs; shown in green): MKK6, MKK4, MKK7, MEK. These MAPKKs in turn phosphorylate and activate the MAPKs, p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), which translocate to the nucleus. There, these MAPKs phosphorylate and activate the transcription factors (activating transcription factor 2 [ATF2], c-Jun, Elk-1 and erythroblastosis twenty-six [Ets]-1; shown in red) that contribute to matrix metalloproteinase (MMP) transcription. IL-1R, IL-1 receptor; IL-1RAcP, IL-1 receptor-associated protein; IRAK, IL-1 receptor activated kinase; SRF, serum response factor; TAB, Tak-binding protein; TRAF, TNF receptor-associated factor.