The Abl family of non-receptor tyrosine kinases encoded by the genes ABL1 and ABL2 are
part of the signaling pathways that control cell proliferation, migration and apoptosis. The activity of
Abl family kinases is tightly controlled through an autoinhibitory mechanism based on intramolecular
interactions controlling the activity of the kinase domain. Activation of Abl kinases is promoted by
phosphorylation by upstream kinases or engagement by interaction partners and results in a conformational
modification of the kinase domain. Abl kinases are frequently deregulated in human leukemias
because of chromosomal abnormalities that lead to the expression of fusion proteins such as BCRAbl1.
No activating Abl mutations have been detected in solid tumors, however in many of them, increased
c-Abl/Arg activity has been revealed. The reported capacity of c-Abl to promote the downregulation
of the CDK inhibitors p27KIP1 and p21CIP1 in hematological as well as in solid tumors offers
an explanation for the mechanism of the mitogenic effect of Abl activation.
Keywords: Abl, apoptosis, Arg, BCR-Abl1, proliferation, SH2, SH3, tyrosine-kinase-inhibitors.
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