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Merck

Controlling Abl: auto-inhibition and co-inhibition?

Nature cell biology (2004-01-06)
Jean Y J Wang
ABSTRACT

Auto-inhibition describes the capacity of proteins to adopt a self-imposed latent conformation. Recently, a crystal structure of the Abl tyrosine kinase has revealed its ability to auto-inhibit. However, a separate body of work suggests that other cellular proteins also inhibit Abl. To reconcile the crystal structure with Abl inhibitors, I propose that Abl is controlled by cellular 'co-inhibitors' that bind Abl, stabilizing the auto-inhibited conformation. The implication of co-inhibition on Abl function is discussed.