c-Myb and v-Myb are differentially phosphorylated by p42mapk in vitro.
The product of the c-myb proto-oncogene is a highly conserved transcription factor that has been shown to function as both a transactivator and repressor. The v-myb oncogenes of E26 leukemia virus and avian myeloblastosis virus (AMV) encode proteins truncated at both the amino and carboxy termini, deleting portions of the DNA-binding and negative regulatory domains present in c-Myb. Similar truncations of c-Myb alter its function, suggesting that the viral proteins lack important regulatory sequences. Interestingly, eight potential sites of phosphorylation by proline-directed protein kinases conserved between the avian, murine and human Myb proteins are clustered in or near the negative regulatory domain of c-Myb. The majority of these sites are deleted in both the E26 and AMV viral proteins. In this paper we show that one proline-directed protein kinase, p42mapk, phosphorylates bacterially synthesized avian and murine c-Myb but not AMV v-Myb in vitro. We find that p42mapk phosphorylates c-Myb on serine and threonine, but not on tyrosine. Furthermore, deletion analysis indicates that the sites of phosphorylation map to the C-terminal negative regulatory domain. We speculate that the inability of v-Myb to be phosphorylated by p42mapk may contribute to its oncogenic properties.
Aziz
N
N
Department of Pharmacology, University of Virginia, Charlottesville 22908.
Wu
J
J
Dubendorff
J W
JW
Lipsick
J S
JS
Sturgill
T W
TW
Bender
T P
TP
D000818:Animals; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D009154:Mutation; D020626:Oncogene Proteins v-myb; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*
C000715470:MAS1 protein, human; D020626:Oncogene Proteins v-myb; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015682:Retroviridae Proteins, Oncogenic; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1