Document Detail


Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site.
MedLine Citation:
PMID:  9053848     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BCR/ABL has a causal role in Philadelphia (Ph)-chromosome positive leukemia. The SH2/SH3 adapter protein CRKL is a major substrate of the deregulated BCR/ABL tyrosine kinase and is aberrantly tyrosine-phosphorylated in Ph-positive leukemia cells. In this study, experiments were pursued to identify and analyse the CRKL phosphorylation site(s). In an in vitro kinase assay, CRKL phosphorylation by the abl kinase was limited to a small region between the two CRKL SH3 domains. Within this region, mutation of tyrosine residue 207 yielded a mutant CRKL which could not be phosphorylated by BCR/ABL. Stable overexpression of CRKL or CRKL-Y207F did not transform NIH3T3 cells, while the Y207F mutation eliminated tyrosine-phosphorylation of CRKL. These studies indicate that Y207 in CRKL represents the major in vivo phosphorylation site. Phosphorylation of Y207 provides a binding site for the CRKL SH2 domain and potentially for other SH2-containing proteins. The Y207F mutation in CRKL did not enhance or decrease association with various target signalling proteins, including SOS or C3G, which interact specifically with the CRKL N-SH3 domain. These findings suggest that complex formation with cellular targets is not modulated by CRKL tyrosine-phosphorylation.
Authors:
R de Jong; J ten Hoeve; N Heisterkamp; J Groffen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  14     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-03-07     Completed Date:  1997-03-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  507-13     Citation Subset:  IM    
Affiliation:
Department of Pathology, Childrens Hospital of Los Angeles, CA 90027, USA.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Adaptor Proteins, Signal Transducing*
Amino Acid Sequence
Animals
COS Cells
Fusion Proteins, bcr-abl / metabolism*
Humans
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
Nuclear Proteins / biosynthesis,  chemistry*,  metabolism*
Phosphoproteins / metabolism
Phosphorylation
Point Mutation
Protein-Tyrosine Kinases / metabolism*
Recombinant Fusion Proteins / biosynthesis
Recombinant Proteins / biosynthesis,  chemistry,  metabolism
Transfection
Tyrosine*
Grant Support
ID/Acronym/Agency:
CA 47456/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/CRKL protein; 0/Fusion Proteins, bcr-abl; 0/Nuclear Proteins; 0/Phosphoproteins; 0/Recombinant Fusion Proteins; 0/Recombinant Proteins; 55520-40-6/Tyrosine; EC 2.7.10.1/Protein-Tyrosine Kinases

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