Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages.
Four p38 mitogen-activated protein kinases (p38alpha, beta, gamma, delta) have been described. To understand the role of p38 family members in inflammation, we determined their relative expression in cells that participate in the inflammatory process. Expression was measured at the level of mRNA by reverse-transcriptase PCR and protein by Western blot analysis. p38alpha was the dominant form of p38 in monocytes; expression of p38delta was low and p38beta was undetected. In macrophages, p38alpha and p38delta were abundant, but p38beta was undetected. p38alpha and p38delta were also expressed by neutrophils, CD4+ T cells, and endothelial cells. Again, p38beta was not detected in neutrophils, although low amounts were present in CD4+ T cells. In contrast, p38beta was abundant in endothelial cells. p38gamma protein was not detected in any cell type, although p38gamma mRNA was present in endothelial cells. Immunokinase assays showed a strong activation of p38alpha and a lesser activation of p38delta in LPS-stimulated macrophages. Abs specific for mono- and dual-phophorylated forms of p38 suggested that LPS induces dual phosphorylation of p38alpha, but primarily mono-phosphorylation of p38delta. IL-1beta activated p38alpha and p38beta in endothelial cells. However, p38alpha was the more activated form based on kinase assays and phosphorylation analysis. Expression and activation patterns of p38alpha in macrophages and endothelial cells suggest that p38alpha plays a major role in the inflammatory response. Additional studies will be needed to define the contribution of p38delta to macrophage, neutrophil, and T cell functions, and of p38beta to signaling in endothelial cells and T cells.
Hale
K K
KK
Department of Biology, Amgen, Boulder, CO 80301, USA.
Trollinger
D
D
Rihanek
M
M
Manthey
C L
CL
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis* / Q000378:metabolism*; D019070:Cell Lineage; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases; D009504:Neutrophils / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases
D017931:DNA Primers; D007527:Isoenzymes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases