Negative regulation of c-abl tyrosine kinase by its variable N-terminal amino acids.
Activation of the oncogenic potential of c-abl proto-oncogene has been correlated with the activation of its tyrosine kinase activity. The oncogenes derived from c-abl, e.g., gag/v-abl in Abelson murine leukemia virus or bcr/abl in chronic myelogenous leukemia, lack N-terminal coding sequences of the normal c-abl gene. In mouse and human cells, two sets of N-terminal amino acids encoded by 5'-variable exons are found in c-abl proteins. To assess the importance of N-terminal deletion in the activation of c-abl tyrosine kinase, a full length or an N-terminal deleted c-abl protein was expressed in bacteria and in monkey COS cells. Measurements of the autokinase activity of these two c-abl proteins showed that deletion of the N-terminal amino acids led to a three to five fold increase of the c-abl tyrosine kinase activity. Thus, the N-terminal deletion is important in the activation of c-abl proto-oncogene.
Wang
J Y
JY
Department of Biology, University of California, San Diego, La Jolla, 92093.
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004790:Enzyme Induction; D004926:Escherichia coli; D015683:Gene Products, gag; D000882:Haplorhini; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016315:Proto-Oncogene Proteins c-abl; D011994:Recombinant Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012191:Retroviridae Proteins / Q000096:biosynthesis; D014764:Viral Proteins / Q000096:biosynthesis
D015683:Gene Products, gag; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D014764:Viral Proteins; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl