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Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins.

Chronic myelogenous leukemia (CML) is a disease characterized by the presence of p210(bcr-abl), a chimeric protein with tyrosine kinase activity. Substrates for p210(bcr-abl) are likely to be involved in the pathogenesis of CML. Here we describe the purification, cDNA cloning, and characterization of a 56-kDa tyrosine phosphorylated protein, p56(dok-2) (Dok-2), from p210(bcr-abl) expressing cells. The human dok-2 cDNA encodes a 412-amino acid protein with a predicted N-terminal pleckstrin homology domain as well as several other features of a signaling molecule, including 13 potential tyrosine phosphorylation sites, six PXXP motifs, and the ability to bind to p120(RasGAP). Dok-2 was shown to be 35% identical to p62(dok-1), a recently identified RasGAP binding protein from CML cells, and analysis of the expressed sequence tag data base revealed the presence of at least four additional proteins containing a Dok homology sequence motif. Dok mRNAs were primarily expressed in tissues of hematopoietic origin. These findings strongly suggest that a family of Dok-related proteins exists that bind to RasGAP and may mediate the effects of p210(bcr-abl) in CML.

Pubmed ID: 9478921


  • Di Cristofano A
  • Carpino N
  • Dunant N
  • Friedland G
  • Kobayashi R
  • Strife A
  • Wisniewski D
  • Clarkson B
  • Pandolfi PP
  • Resh MD


The Journal of biological chemistry

Publication Data

February 27, 1998

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 64593

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary
  • DNA-Binding Proteins
  • Fusion Proteins, bcr-abl
  • GTPase-Activating Proteins
  • Hematopoietic Stem Cells
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Mice
  • Molecular Sequence Data
  • Phosphoproteins
  • Phosphorylation
  • Protein Binding
  • Protein-Tyrosine Kinases
  • Proteins
  • RNA-Binding Proteins
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Tissue Distribution