Abelson-transformed fibroblasts contain nuclear phosphotyrosyl-proteins which preferentially bind to murine DNA.
Protein-tyrosine kinases, either in the form of growth-factor receptors or as the polypeptide products of oncogenes, appear to be important in the regulation of cell growth and transformation. A major question, however, is how their substrates mediate changes in gene expression (reviewed in refs 6-8). Because binding of proteins to specific DNA sequences represents the most direct mechanism for regulating transcription, we have investigated the possibility that some DNA-binding proteins may be substrates of protein-tyrosine kinases. Here, we present evidence for nuclear phosphotyrosyl-proteins in murine fibroblasts transformed by the v-abl protein-tyrosine kinase. Furthermore, we have found that these proteins are not significantly phosphorylated in normal NIH 3T3 cells. Finally, using affinity competition chromatography with bacterial and mouse DNA, we have demonstrated that some of these proteins preferentially bind to mouse DNA. The identification of phosphotyrosyl-proteins with selective DNA-binding properties suggests a possible mechanism through which protein-tyrosine kinases may effect changes in gene transcription.
D000011:Abelson murine leukemia virus / Q000201:enzymology*; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D002472:Cell Transformation, Viral; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology*; D009052:Leukemia Virus, Murine / Q000201:enzymology*; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology; D009856:Oncogene Proteins, Viral / Q000502:physiology; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D014764:Viral Proteins / Q000502:physiology
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases