Functional analysis of phosphorylation at serine 532 of human c-Myb by MAP kinase

Biol Chem. 1996 Nov;377(11):721-30. doi: 10.1515/bchm3.1996.377.11.721.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Genes, ras
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Jurkat Cells
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-myb
  • Serine*
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Transcription, Genetic

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myb
  • Trans-Activators
  • Serine
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases