Regulation of STAT3 by direct binding to the Rac1 GTPase.
The signal transducers and activators of transcription (STAT) transcription factors become phosphorylated on tyrosine and translocate to the nucleus after stimulation of cells with growth factors or cytokines. We show that the Rac1 guanosine triphosphatase can bind to and regulate STAT3 activity. Dominant negative Rac1 inhibited STAT3 activation by growth ... factors, whereas activated Rac1 stimulated STAT3 phosphorylation on both tyrosine and serine residues. Moreover, activated Rac1 formed a complex with STAT3 in mammalian cells. Yeast two-hybrid analysis indicated that STAT3 binds directly to active but not inactive Rac1 and that the interaction occurs via the effector domain. Rac1 may serve as an alternate mechanism for targeting STAT3 to tyrosine kinase signaling complexes.
Mesh Terms:
Amino Acid Substitution, Animals, COS Cells, Cell Line, Cercopithecus aethiops, DNA-Binding Proteins, Enzyme Activation, Epidermal Growth Factor, Gene Expression Regulation, Genes, Reporter, Genetic Vectors, Guanine Nucleotide Exchange Factors, Humans, Janus Kinase 2, Mutation, Neoplasm Proteins, Phosphorylation, Phosphoserine, Phosphotyrosine, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Rats, STAT3 Transcription Factor, Signal Transduction, Trans-Activators, Transfection, Two-Hybrid System Techniques, rac1 GTP-Binding Protein
Amino Acid Substitution, Animals, COS Cells, Cell Line, Cercopithecus aethiops, DNA-Binding Proteins, Enzyme Activation, Epidermal Growth Factor, Gene Expression Regulation, Genes, Reporter, Genetic Vectors, Guanine Nucleotide Exchange Factors, Humans, Janus Kinase 2, Mutation, Neoplasm Proteins, Phosphorylation, Phosphoserine, Phosphotyrosine, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Rats, STAT3 Transcription Factor, Signal Transduction, Trans-Activators, Transfection, Two-Hybrid System Techniques, rac1 GTP-Binding Protein
Science
Date: Oct. 06, 2000
PubMed ID: 11021801
View in: Pubmed Google Scholar
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