Examination of the role of MAP kinase in the response of macrophages to lipopolysaccharide.
Although the mechanism by which macrophages and other mammalian cells recognize LPS is still only partially understood, there has been considerable recent progress in unraveling the mechanisms by which putative cell surface LPS receptors transmit information of ligand binding to the interior of the cell. In macrophages, LPS induces protein tyrosine phosphorylation of a handful of proteins. We have identified two of the more prominent phosphorylated proteins as p42 and p44 MAP kinases. In addition, we have examined the role of MAP kinases in the macrophage response to LPS by utilizing a regulatable form of Raf-1 to activate MAP kinases independently of LPS. These experiments suggest that MAP kinases participate in LPS signaling, but also demonstrate that activation of MAP kinases cannot account for all of the intracellular events triggered by LPS. Therefore LPS must activate other signaling events that contribute to NF-kappa B activation and TNF-alpha mRNA accumulation and protein secretion.
Department of Microbiology & Immunology, G.W. Hooper Foundation, University of California, San Francisco 94143-0552, USA.
A L
AL
DeFranco
J
J
Hambleton
M
M
McMahon
S L
SL
Weinstein
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D008070:Lipopolysaccharides; D016328:NF-kappa B; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases