3BP-2: A novel substrate of the FLT3 receptor tyrosine kinase

摘要

Flt3 is a receptor tyrosine kinase expressed on early committed and uncommitted hematopoietic cells. The ligand for this receptor supports B cell differentiation from uncommitted progenitor cells. In an attempt to understand the mechanism of Flt3 signalling, I have identified the protein 3BP-2 as a novel Flt3 substrate. 3BP-2 is a linker molecule which was cloned based on its ability to bind the c-Abl protein in vitro. I have mapped the 3BP-2 binding site to residue Y769 of Flt3 by blocking the Flt3:3BP-2 interaction with a Y769F mutant of the receptor. In addition, I have shown that the Y769F mutant receptor is hypersensitive to ligand stimulation as compared to the wild type protein in mitogenesis assays. These data imply that residue Y769 is a site of interaction with 3BP-2, and that a growth inhibitory signal is mediated through this site on Flt3.