Structural basis for the autoinhibition of c-Abl tyrosine kinase

• Published in: Cell (ISSN: 0092-8674), vol. 112, num. 6, p. 859-71
• Elsevier, 2003

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.

Note:

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

Reference

• EPFL-ARTICLE-164348
• doi:10.1016/S0092-8674(03)00194-6

Record created on 2011-03-21, modified on 2017-05-12