RRC ID 72365
Author Nosaka Y, Arai A, Kanda E, Akasaki T, Sumimoto H, Miyasaka N, Miura O.
Title Rac is activated by tumor necrosis factor alpha and is involved in activation of Erk.
Journal Biochem Biophys Res Commun
Abstract Tumor necrosis factor alpha (TNFalpha) activates various signal transduction pathways including those involving phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinases (Erk), c-Jun N-terminal protein kinases (JNK), and p38 kinases. Using the Rac binding domain of PAK (PAK-RBD) as an activation-specific probe, here we demonstrate that TNFalpha very rapidly and transiently activates the Rho family GTPase Rac in L929 cells. The PI3K inhibitor LY294002 significantly inhibited TNFalpha activation of Rac as well as Erk and abolished that of the PI3K target Akt, without showing any inhibitory effects on JNK and p38 activation. Furthermore, TNFalpha activation of Erk was abolished by a dominant negative Rac mutant, Rac17N, or by an activated Rac mutant, Rac12V. These findings suggest that Rac is activated by a mechanism that is at least partly dependent on PI3K in TNFalpha stimulated cells and plays a critical role in activation of the Erk signaling pathway.
Volume 285(3)
Pages 675-9
Published 2001-7-20
DOI 10.1006/bbrc.2001.5222
PII S0006-291X(01)95222-2
PMID 11453646
MeSH Animals Cell Line Chromones / pharmacology Enzyme Activation / drug effects Enzyme Activation / physiology Enzyme Inhibitors / pharmacology Fibrosarcoma / metabolism Genes, Dominant Imidazoles / pharmacology Mice Mitogen-Activated Protein Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / metabolism* Morpholines / pharmacology Mutagenesis, Site-Directed Phosphatidylinositol 3-Kinases / metabolism Phosphoinositide-3 Kinase Inhibitors Protein Serine-Threonine Kinases* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-akt Pyridines / pharmacology Transfection Tumor Necrosis Factor-alpha / metabolism* Tumor Necrosis Factor-alpha / pharmacology p38 Mitogen-Activated Protein Kinases rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism*
IF 2.985
Human and Animal Cells L929