p62(dok): a constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells

Cell. 1997 Jan 24;88(2):197-204. doi: 10.1016/s0092-8674(00)81840-1.

Abstract

Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p210(bcr-abl) protein possessing elevated protein tyrosine kinase activity relative to normal c-abl tyrosine kinase. Hematopoietic progenitors isolated from CML patients in the chronic phase contain a constitutively tyrosine-phosphorylated protein that migrates at 62 kDa by SDS-PAGE and associates with the p120 ras GTPase-activating protein (GAP). We have purified p62(dok) from a hematopoietic cell line expressing p210(bcr-abl). p62(dok) is a novel protein with features of a signaling molecule. Association of p62(dok) with GAP correlates with its tyrosine phosphorylation. p62(dok) is rapidly tyrosine-phosphorylated upon activation of the c-Kit receptor, implicating it as a component of a signal transduction pathway downstream of receptor tyrosine kinases.

Publication types

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

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Cloning, Molecular
  • DNA-Binding Proteins*
  • Electrophoresis, Polyacrylamide Gel
  • Fusion Proteins, bcr-abl / metabolism
  • GTPase-Activating Proteins
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-kit / metabolism
  • RNA-Binding Proteins*
  • Signal Transduction
  • Stem Cell Factor / metabolism
  • Tumor Cells, Cultured
  • ras GTPase-Activating Proteins
  • src Homology Domains
  • src-Family Kinases

Substances

  • DNA-Binding Proteins
  • DOK1 protein, human
  • GAP-associated protein p62
  • GTPase-Activating Proteins
  • Phosphoproteins
  • Proteins
  • RNA-Binding Proteins
  • Stem Cell Factor
  • ras GTPase-Activating Proteins
  • Phosphotyrosine
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • CSK Tyrosine-Protein Kinase
  • Fusion Proteins, bcr-abl
  • src-Family Kinases
  • CSK protein, human

Associated data

  • GENBANK/U70987