The ezrin-like family of tyrosine kinase substrates: receptor-specific pattern of tyrosine phosphorylation and relationship to malignant transformation

Oncogene. 1993 May;8(5):1335-45.

Abstract

A method for the isolation of tyrosine kinases substrates was developed. The method takes advantage of immuno-affinity purification of an entire set of proteins phosphorylated by tyrosine kinases, followed by generation of antisera against the purified protein pool and immunological screening of bacterial expression libraries with these antisera. By applying this methodology to the study of the phosphorylation events triggered by activation of the epidermal growth factor receptors, we have isolated several cDNAs encoding novel putative tyrosine kinase substrates. One of these cDNAs encodes radixin, a protein belonging to the band 4.1 family of proteins and highly related to ezrin and moesin. We demonstrated that, despite a high degree of relatedness, these three proteins exhibit a distinct receptor-specific pattern of phosphorylation, raising the possibility that they might mediate receptor-specific cellular changes. In addition the generation of antibodies specific for either radixin, ezrin or moesin allowed us to show that a previously described tumor transplantation antigen is indeed ezrin, thus implicating this protein in the determination of the biological phenotype of certain tumors.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / analysis
  • Base Sequence
  • Blood Proteins / genetics
  • Blood Proteins / metabolism
  • Cell Transformation, Neoplastic*
  • Cloning, Molecular
  • Cytoskeletal Proteins*
  • ErbB Receptors / metabolism
  • Histocompatibility Antigens / analysis
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Microfilament Proteins*
  • Molecular Sequence Data
  • Neuropeptides*
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Proteins / metabolism
  • Rabbits
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Tyrosine / metabolism*

Substances

  • Antigens, Neoplasm
  • Blood Proteins
  • Cytoskeletal Proteins
  • Histocompatibility Antigens
  • Membrane Proteins
  • Microfilament Proteins
  • Neuropeptides
  • Phosphoproteins
  • Proteins
  • erythrocyte membrane band 4.1 protein
  • erythrocyte membrane protein band 4.1-like 1
  • ezrin
  • tumor-associated transplantation antigen
  • moesin
  • radixin
  • Tyrosine
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor