A mechanistic design principle for protein tyrosine kinase sensors: application to a validated cancer target.

A new mechanistic principle for reporting the phosphorylation of tyrosine is described, which should prove applicable to even the most fastidious of protein tyrosine kinases, as demonstrated by the acquisition of a fluorescent sensor for the extraordinarily demanding anaplastic lymphoma kinase.

Characterization of some molecular mechanisms governing autoactivation of the catalytic domain of the anaplastic lymphoma kinase.

NPM/ALK is an oncogenic fusion protein expressed in approximately 50% of anaplastic large cell lymphoma cases. It derives from the t(2;5)(p23;q35) chromosomal translocation that fuses the catalytic domain of the tyrosine kinase, anaplastic lymphoma kinase (ALK), with the dimerization domain of the ubiquitously expressed nucleophosmin (NPM) protein. Dimerization of the ALK kinase domain leads to its autophosphorylation and constitutive activation.