Induction Of Beta-Catenin By The Suppression Of Signal Regulatory Protein Alpha 1 In K562 Cells

The signal regulatory protein (SIRP) alpha 1 is a cell surface receptor expressed predominantly in monocytes, granulocytes, dendritic cells, as well as hematopoietic stem cells. In contrast, SIRP alpha 1 expression is significantly reduced in the majority of myeloid malignancies. SIRP alpha 1 is a negative regulator of signaling and its reduced expression is considered to play a role in the pathogenesis of these diseases through aberrant signaling. To identify SIRP alpha 1 downstream target genes, we established SIRP alpha 1-knockdown chronic myeloid leukemia K562 (K562SIRP alpha 1KD) cells expressing reduced levels of SIRP alpha 1 by stably transfecting SIRP alpha 1 siRNAs. Microarray analysis demonstrated that several genes, including beta-catenin, were significantly induced in K562SIRP alpha 1KD cells. Real-time PCR and Western blot analyses, confirmed the induction of this gene. Phosphorylation of Ser9 of glycogen synthesis kinase (GSK) -3 beta, results in the inactivation of GSK-3 beta, leading to the induction of beta-catenin. We found significant phosphorylation of extracellular signal-regulated kinase (ERK), Akt, as well as of GSK-3 beta-Ser9, which may play a role in the up-regulation of beta-catenin in K562SIRPa1KD cells. To our knowledge, this is a first report demonstrating the relationships between SIRP alpha 1 and beta-catenin in leukemia cells.