Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA.
The proto-oncogene c-abl encodes a protein tyrosine kinase that is localized in the cytoplasm and the nucleus. The large carboxyl-terminal segment of c-Abl was found to contain a DNA-binding domain that was necessary for the association of c-Abl with chromatin. The DNA-binding activity of c-Abl was lost during mitosis when the carboxyl-terminal segment became phosphorylated. In vitro phosphorylation of the DNA-binding domain by cdc2 kinase abolished DNA binding. Homozygous mutant mice expressing a c-Abl tyrosine kinase without the DNA-binding domain have been reported to die of multiple defects at birth. Thus, binding of the c-Abl tyrosine kinase to DNA may be essential to its biological function.
Kipreos
E T
ET
Department of Biology, University of California San Diego, La Jolla 92093-0116.
Wang
J Y
JY
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000502:physiology*; D002846:Chromatography, Affinity; D004247:DNA / Q000378:metabolism*; D016313:Genes, abl; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D010769:Phosphothreonine; D010768:Phosphoserine; D004247:DNA; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl