Functional analysis of phosphorylation at serine 532 of human c-Myb by MAP kinase.
The c-myb proto-oncogene encodes a transcription factor that is implicated in regulatory events during hematopoiesis. It contains negative regulatory domains at both the amino- and carboxy-termini. Here we describe that human c-Myb can be phosphorylated by mitogen-activated protein kinases (MAPK's) at serine 532 of the carboxy (C-) terminal regulatory domain in vitro. This serine residue can also be phosphorylated in vivo upon serum-stimulation of Jurkat cells. Expression of a constitutively active form of Ras together with c-Myb in transient transfection experiments had no effect on the transcriptional activity of c-Myb, while expression of a polypeptide containing the c-Myb C-terminal domain stimulated c-Myb activity. This effect is reduced upon MAPK-dependent phosphorylation of serine 532. Our data suggest that the MAPK-dependent state of phosphorylation modifies the cellular function of c-Myb by modulating its interaction with a putative inhibitory factor.
Vorbrueggen
G
G
Institut für Medizinische Virologie, Universität Zürich, Switzerland.
Lovrić
J
J
Moelling
K
K
D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D011905:Genes, ras; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D012694:Serine; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D012694:Serine; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases