p38α MAPK can positively or negatively regulate Rac-1 activity depending on the presence of serum

The small GTP-ase Rac-1 can trigger p38 MAPK activation and, in turn, p38α can regulate signalling pathways that potentially impinge on Rac-1 activity. We have investigated the cross-talk between p38α and Rac-1 and found that p38α regulates the association between Rac-1 and caveolin-1 in serum-deprived cardiomyocytes. This interaction depends on cell attachment and correlates with higher levels of active Rac-1. Actin organization might regulate the formation of Rac-1–caveolin-1 complexes. In contrast, the Rac-1–caveolin-1 interaction is almost undetectable in the presence of serum, where Rac-1 activity is negatively regulated by p38α. Our results indicate that p38α can differentially contribute to Rac-1 activation depending on the presence of serum.