Identification of complex formation between two intracellular tyrosine kinase substrates: human c-Rel and the p105 precursor of p50 NF-kappa B

Oncogene. 1992 Nov;7(11):2095-104.

Abstract

Immune complexes of the product of the c-rel protooncogene and of p105, the p50 NF-kappa B precursor, isolated from human T-lymphoblastoid cell lines are comprised of multiple proteins. Only p105 and human c-Rel (hc-Rel) are common to complexes precipitated with antiserum directed against either p105 or hc-Rel. Both proteins are inducible by phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) and their subcellular distribution is affected by this induction. We demonstrate that the Rel immune complex contains a protein with a molecular weight in the 40 kDa range (p40) which apparently is exclusively cytoplasmic. We were not able to detect p40 in the p105 immune complex, though hc-Rel is present. This indicates that hc-Rel exists in different multi-protein complexes and fits a model of functional regulation mediated by differential protein-protein interaction. We also demonstrate considerable isoform diversity of both hc-Rel and p105. We show that this heterogeneity is, in part, the result of phosphorylation. Furthermore, we demonstrate that p105 and hc-Rel are tyrosine kinase substrates. This finding indicates a role for both proteins in intracellular signal transduction pathways which are modulated by modification of their phosphorylation status.

Publication types

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

MeSH terms

  • Humans
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Phytohemagglutinins
  • Protein Precursors / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-rel
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • NF-kappa B
  • Phytohemagglutinins
  • Protein Precursors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • Protein-Tyrosine Kinases
  • Tetradecanoylphorbol Acetate