Nuclear localization of p185neu tyrosine kinase and its association with transcriptional transactivation.
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.
Xie
Y
Y
Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Hung
M C
MC
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000096:biosynthesis / Q000378:metabolism; D005786:Gene Expression Regulation; D018734:Genes, erbB-2; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C052130:GAL4 protein, S cerevisiae