Disabled-2 Small Interfering Rna Modulates Cellular Adhesive Function and Mapk Activity during Megakaryocytic Differentiation of K562 Cells

Abstract

Previous studies have shown that Disabled-2 (DAB2) is up- regulated during megakaryocytic differentiation of human K 562 cells. To delineate the consequences of DAB2 induction, a DNA vector-based small interfering RNA (siRNA) was designed to intervene in DAB2 expression. We found that DAB2 siRNA specifically inhibited DAB2 induction, resulting in the modulation of cell-cell adhesion and mitogen-activated protein kinase ( MAPK) phosphorylation. The morphological changes and 03 integrin expression associated with megakaryocytic differentiation were not affected. Since the MAPK pathway has been shown to involve DAB2 induction [Tseng et al., Biochem. Biophys. Res. Commun. 285 (2001) 129-135], our results suggest a reciprocal regulation between DAB2 and MAPK in the differentiation of K562 cells. In addition, we have demonstrated for the first time that DAB2 siRNA is a valuable tool for unveiling the biological consequences of DAB2 expression.