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Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages


Molecular and Cellular Biology 15 (1995), No.1, pp.466-475
ISSN: 0270-7306
Journal Article
Fraunhofer ITA ( ITEM) ()
amino acid; biochemistry; cell line; DNA binding protein; enzyme activation; growth factor; guanosine triphosphatase; macrophage; molecular biology; mouse; phosphorylation; protein kinase

Mitogen-activated protein kinases (MAPKs) are activated upon a variety of extracellular stimuli in different cells. In macrophages, colony-stimulating factor 1 (CSF-1) stimulates proliferation, while bacterial lipopolysaccharide (LPS) inhibits cell growth and causes differentiation and activation. Both CSF-1 and LPS rapidly activate the MAPK network and induce the phosphorylation of two distinct ternary complex factors (TCFs), TCF/Elk and TCF/SAP. CSF-1, but not LPS, stimulated the formation of p21ras. GTP complexes. Expression of a dominant negative ras mutant reduced, but did not abolish, CSF-1-mediated stimulation of MEK and MAPK. In contrast, activation of the MEK kinase Raf-1 was Ras independent. Treatment with the phosphatidylcholine-specific phospholipase C inhibitor D609 suppressed LPS-mediated, but not CSF-1-mediated, activation of Raf-1, MEK, and MAPK. Similarly, down-regulation or inhibition of protein kinase C blocked MEK and MAPK induction by LPS.