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

Overview

abstract

  • 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.

publication date

  • February 27, 1998

Research

keywords

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • Fusion Proteins, bcr-abl
  • Phosphoproteins
  • Protein-Tyrosine Kinases
  • Proteins
  • RNA-Binding Proteins

Identity

Scopus Document Identifier

  • 0032570581

Digital Object Identifier (DOI)

  • 10.1074/jbc.273.9.4827

PubMed ID

  • 9478921

Additional Document Info

volume

  • 273

issue

  • 9