Molecular cloning and characterization of p56(dok-2) defines a new family of RasGAP-binding proteins Journal Article
| Authors: | Di Cristofano, A.; Carpino, N.; Dunant, N.; Friedland, G.; Kobayashi, R.; Strife, A.; Wisniewski, D.; Clarkson, B.; Pandolfi, P. P.; Resh, M. D. |
| Article Title: | Molecular cloning and characterization of p56(dok-2) defines a new family of RasGAP-binding proteins |
| 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. |
| Keywords: | signal transduction; protein phosphorylation; dna-binding proteins; binding affinity; proteins; animals; mice; gene expression; cell line; protein binding; enzyme activity; tyrosine; phosphorylation; data base; molecular cloning; cloning, molecular; rna-binding proteins; amino acid sequence; molecular sequence data; sequence homology, amino acid; tissue distribution; protein purification; carrier proteins; hematopoietic stem cells; adaptor proteins, signal transducing; phosphoproteins; gtpase-activating proteins; protein-tyrosine kinases; sequence homology; protein family; fusion proteins, bcr-abl; dna, complementary; leukemia, myeloid, chronic; humans; priority journal; article; phosphorylase |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 273 |
| Issue: | 9 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1998-02-27 |
| Start Page: | 4827 |
| End Page: | 4830 |
| Language: | English |
| DOI: | 10.1074/jbc.273.9.4827 |
| PUBMED: | 9478921 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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120Resh -
37Wisniewski -
220Clarkson -
41
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2
Dunant
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