MOLECULAR-CLONING AND CHARACTERIZATION OF P56(DOK-2) DEFINES A NEW FAMILY OF RASGAP-BINDING PROTEINS

Citation
A. Dicristofano et al., MOLECULAR-CLONING AND CHARACTERIZATION OF P56(DOK-2) DEFINES A NEW FAMILY OF RASGAP-BINDING PROTEINS, The Journal of biological chemistry, 273(9), 1998, pp. 4827-4830
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
9
Year of publication
1998
Pages
4827 - 4830
Database
ISI
SICI code
0021-9258(1998)273:9<4827:MACOPD>2.0.ZU;2-V
Abstract
Chronic myelogenous leukemia (CML) is a disease characterized by the p resence of p210(bcr-abl), a chimeric protein with tyrosine kinase acti vity. Substrates for p210(bcr-abl) are likely to be involved in the pa thogenesis of CML. Here we describe the purification, cDNA cloning, an d characterization of a 56-kDa tyrosine phosphorylated protein, p56(do k-2) (Dok-2), from p210(bcr-abl) ex pressing cells, The human dok-2 cD NA encodes a 412-amino acid protein with a predicted N-terminal plecks trin homology domain as well as several other features of a signaling molecule, including 13 potential tyrosine phosphorylation sites, six P XXP motifs, and the ability to bind to p120(RasGAP). Dok-2 was shown t o be 35% identical to p62(dok-1), a recently identified RasGAP binding protein from CML cells, and analysis of the expressed sequence tag da ta base revealed the presence of at least four additional proteins con taining a Dok homology sequence motif. Dok mRNAs were primarily expres sed in tissues of hematopoietic origin. These findings strongly sugges t that a family of Dok-related proteins exists that bind to RasGAP and may mediate the effects of p210(bcr-abl) in CML.