6533b834fe1ef96bd129d8c3

RESEARCH PRODUCT

Role of SHP2 for FLT3-dependent proliferation and transformation in 32D cells.

subject

description

Fms-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase, which plays a role in proliferation and differentiation of B-cell progenitors, myelomonocytic and dendritic cells, as well as in the maintenance of pluripotent hematopoietic stem cells (reviewed in Stirewalt and Radich,1and Schmidt-Arras et al.2). Recently, FLT3 has received much attention as an important oncoprotein. Mutations in FLT3 that lead to constitutive activation are among the most common molecular lesions found in acute myeloid leukemia.3 The most prevalent type of mutations result in internal tandem duplications (ITD) of amino-acid stretches in the juxtamembrane domain of FLT3. FLT3-ITD is constitutively and highly active, can transform myeloid cell lines in vitro4 and can induce a myeloproliferative syndrome. Wild-type FLT3 and FLT3-ITD exhibit qualitative differences in signal transduction. Notably, while FLT3-ITD strongly and directly activates STAT5, ligand-activated wild-type FLT3 is a comparatively weak STAT5 activator (reviewed in Choudhary et al.5). The mechanisms of differential signal transduction are incompletely understood.