p38alpha 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, p38alpha can regulate signalling pathways that potentially impinge on Rac-1 activity. We have investigated the cross-talk between p38alpha and Rac-1 and found that p38alpha 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 p38alpha. Our results indicate that p38alpha can differentially contribute to Rac-1 activation depending on the presence of serum.
Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, UCM, Ciudad Universitaria, 28040 Madrid, Spain.
Susana
S
Zuluaga
Alvaro
A
Gutiérrez-Uzquiza
Paloma
P
Bragado
Alberto
A
Alvarez-Barrientos
Manuel
M
Benito
Angel R
AR
Nebreda
Almudena
A
Porras
D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019085:Fluorescent Antibody Technique, Direct; D015971:Gene Expression Regulation, Enzymologic; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044967:Serum / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D051242:Caveolin 1; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D048308:Mitogen-Activated Protein Kinase 14; D020830:rac1 GTP-Binding Protein; C093642:SB 203580