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research article

Structural basis for the autoinhibition of c-Abl tyrosine kinase

Nagar, Bhushan
•
Hantschel, Oliver  
•
Young, Matthew A.
Show more
2003
Cell

c-Abl is normally regulated by an autoinhibitory mechanism, the disruption of which leads to chronic myelogenous leukemia. The details of this mechanism have been elusive because c-Abl lacks a phosphotyrosine residue that triggers the assembly of the autoinhibited form of the closely related Src kinases by internally engaging the SH2 domain. Crystal structures of c-Abl show that the N-terminal myristoyl modification of c-Abl 1b binds to the kinase domain and induces conformational changes that allow the SH2 and SH3 domains to dock onto it. Autoinhibited c-Abl forms an assembly that is strikingly similar to that of inactive Src kinases but with specific differences that explain the differential ability of the drug STI-571/Gleevec/imatinib (STI-571) to inhibit the catalytic activity of Abl, but not that of c-Src.

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Type
research article
DOI
10.1016/S0092-8674(03)00194-6
Author(s)
Nagar, Bhushan
Hantschel, Oliver  
Young, Matthew A.
Scheffzek, Klaus
Veach, Darren
Bornmann, William
Clarkson, Bayard
Superti-Furga, Giulio
Kuriyan, John
Date Issued

2003

Publisher

Elsevier

Published in
Cell
Volume

112

Issue

6

Start page

859

End page

71

Note

Comment in: Cell. 2003 Mar 21;112(6):737-40

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
UPHAN  
Available on Infoscience
March 21, 2011
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/65492
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