Abstract
The rat neu protooncogene encodes a 185 kD transmembrane protein (p185neu), which is a member of the epidermal growth factor receptor (EGFr) family. In searching for the signaling transducer of p185neu by using a two-hybrid selection system, we found, surprisingly, that the cytoplasmic domain of p185neu, when fused to the DNA-binding domain of GAL4 (amino acids 1-147), functioned as a transcriptional activator. We subsequently observed nuclear localization of p185neu. Interestingly, nuclear p185neu has a much higher extent of tyrosine phosphorylation than its nonnuclear counterpart. Our results suggest that a transmembrane receptor tyrosine kinase may enter the nucleus and be involved in transcriptional activation. This novel finding unveils a clue in the understanding of the mechanism of receptor tyrosine kinase-mediated signal transduction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line
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Cell Nucleus / metabolism*
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DNA-Binding Proteins
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Fluorescent Antibody Technique
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Fungal Proteins / biosynthesis
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Fungal Proteins / metabolism
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Gene Expression Regulation*
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Genes, erbB-2*
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Plasmids
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Promoter Regions, Genetic
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Protein-Tyrosine Kinases / analysis
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Protein-Tyrosine Kinases / biosynthesis
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Protein-Tyrosine Kinases / metabolism*
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Rats
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Receptor, ErbB-2 / analysis
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Receptor, ErbB-2 / biosynthesis
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Receptor, ErbB-2 / metabolism*
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Recombinant Fusion Proteins / analysis
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Sequence Deletion
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Signal Transduction
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Transcription Factors*
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Transcription, Genetic*
Substances
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DNA-Binding Proteins
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Fungal Proteins
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GAL4 protein, S cerevisiae
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Protein-Tyrosine Kinases
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Receptor, ErbB-2