Structural basis for the autoinhibition of c-Abl tyrosine kinase. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • March 21, 2003

Research

keywords

  • Proto-Oncogene Proteins c-abl

Identity

Scopus Document Identifier

  • 0344626926

PubMed ID

  • 12654251

Additional Document Info

volume

  • 112

issue

  • 6