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

Research output: Contribution to journalArticle

114 Citations (Scopus)

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

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Cloning
Molecular Cloning
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Carrier Proteins
Tyrosine
Proteins
Complementary DNA
Expressed Sequence Tags
Sequence Homology
Phosphorylation
Protein-Tyrosine Kinases
Organism Cloning
Purification
Databases
Amino Acids
Messenger RNA
Tissue
Molecules
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular cloning and characterization of p56(dok-2) defines a new family of RasGAP-binding proteins. / Di Cristofano, Antonio; Carpino, Nick; Dunant, Nicolas; Friedland, Gayle; Kobayashi, Ryuji; Strife, Annabel; Wisniewski, David; Clarkson, Bayard; Pandolfi, Pier Paolo; Resh, Marilyn D.

In: Journal of Biological Chemistry, Vol. 273, No. 9, 27.02.1998, p. 4827-4830.

Research output: Contribution to journalArticle

Di Cristofano, A, Carpino, N, Dunant, N, Friedland, G, Kobayashi, R, Strife, A, Wisniewski, D, Clarkson, B, Pandolfi, PP & Resh, MD 1998, 'Molecular cloning and characterization of p56(dok-2) defines a new family of RasGAP-binding proteins', Journal of Biological Chemistry, vol. 273, no. 9, pp. 4827-4830. https://doi.org/10.1074/jbc.273.9.4827
Di Cristofano, Antonio ; Carpino, Nick ; Dunant, Nicolas ; Friedland, Gayle ; Kobayashi, Ryuji ; Strife, Annabel ; Wisniewski, David ; Clarkson, Bayard ; Pandolfi, Pier Paolo ; Resh, Marilyn D. / Molecular cloning and characterization of p56(dok-2) defines a new family of RasGAP-binding proteins. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 9. pp. 4827-4830.
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