Phosphorylation of the TAL1 oncoprotein by the extracellular-signal-regulated protein kinase ERK1

Mol Cell Biol. 1993 Feb;13(2):801-8. doi: 10.1128/mcb.13.2.801-808.1993.

Abstract

Alteration of the TAL1 gene is the most common genetic lesion found in T-cell acute lymphoblastic leukemia. TAL1 encodes phosphoproteins, pp42TAL1 and pp22TAL1, that represent phosphorylated versions of the full-length (residues 1 to 331) and truncated (residues 176 to 331) TAL1 gene products, respectively. Both proteins contain the basic helix-loop-helix motif, a DNA-binding and protein dimerization motif common to several known transcriptional regulatory factors. We now report that serine residue 122 (S122) is a major phosphorylation site of pp42TAL1 in leukemic cell lines and transfected COS1 cells. In vivo phosphorylation of S122 is induced by epidermal growth factor with a rapid time course that parallels activation of the ERK/MAP2 protein kinases. Moreover, S122 is readily phosphorylated in vitro by the extracellular signal-regulated protein kinase ERK1. These data suggest that TAL1 residue S122 serves as an in vivo substrate for ERK/MAP2 kinases such as ERK1. Therefore, S122 phosphorylation may provide a mechanism whereby the properties of TAL1 polypeptides can be modulated by extracellular stimuli.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Line, Transformed
  • Chlorocebus aethiops
  • DNA-Binding Proteins / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Humans
  • Leukemia
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Peptide Mapping
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors*
  • Tumor Cells, Cultured

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors
  • TAL1 protein, human
  • Epidermal Growth Factor
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases