Molecular cloning and characterization of p56(dok-2) defines a new family of RasGAP-binding proteins

Antonio Di Cristofano, Nick Carpino, Nicolas Dunant, Gayle Friedland, Ryuji Kobayashi, Annabel Strife, David Wisniewski, Bayard Clarkson, Pier Paolo Pandolfi, Marilyn D. Resh

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115 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4827-4830
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number9
DOIs
StatePublished - Feb 27 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Di Cristofano, A., Carpino, N., Dunant, N., Friedland, G., Kobayashi, R., Strife, A., Wisniewski, D., Clarkson, B., Pandolfi, P. P., & Resh, M. D. (1998). Molecular cloning and characterization of p56(dok-2) defines a new family of RasGAP-binding proteins. Journal of Biological Chemistry, 273(9), 4827-4830. https://doi.org/10.1074/jbc.273.9.4827