Role of mitogen- and stress-activated kinases in inflammatory arthritis

Figure 1 Schematic representation of human mitogen- and stress-activated protein kinase 1 activation. A: MAPKs bind to the MAPK-docking site in the MSK C-terminal domain (blue); B: Human MSK1 is activated by MAPK-dependent phosphorylation at Ser360, Thr581 and Thr700 located in the C-terminal domain (green); C: Phosphorylation of the C-terminal domain induces a conformational change in MSK1, which permits autophosphorylation at Ser212, Ser376 and Ser381 by the C-terminal kinase domain (red); D: Phosphorylation of MSK substrate (validated substrates include CREB, ATF-1, p65, H3, HMGN1 and Trim7) by the N-terminal kinase domain (black). MSK1: Mitogen- and stress-activated protein kinase 1; MAPK: Mitogen-activated protein kinases; CREB: cAMP response element-binding protein; ATF-1: Activating transcription factor 1; HMGN1: High mobility group nucleosome binding domain 1.