Nck Beta Adapter Protein Coordinates Bcr-Abl/Sam68 Intermolecular Interaction

Background: Philadelphia positive (Ph+) disorders, such as Chronic Myelogenous Leukemia (CML) are characterized by the presence of abnormal chromosome rising from translocation between chromosome 9 and 22 thus giving birth to a chimeric oncogenic protein named Bcr-Abl. This oncogenic kinase displays constitutive tyrosine kinase activity which leads to tyrosine residues autophosphorylation, in turn recruiting SH2 and/or PTB containing proteins. In the last decade Bcr-Abl targeted therapy has been successfully employed and, among currently available drugs inhibiting Bcr-Abl activity, Imatinb mesylate represents the most efficient. Despite the huge amount of data reporting the effects of Imatinib on signal transduction pathways (for example ERK1/2 and PI3K activation, CrkL phosphorylation etc…) in Ph+ leukemic cells rather few experimental evidences are available on the effects of Imatinib on adapter molecules. Therefore we are currently attempting to investigate such field.