RPTP mu tyrosine phosphatase promotes adipogenic differentiation via modulation of p120 catenin phosphorylation

Abstract

Adipocyte differentiation can be regulated by the combined activity of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). In particular, PTPs act as key regulators in differentiation-associated signaling pathways. We recently found that receptor-type PTP mu (RPTP mu) expression is markedly increased during the adipogenic differentiation of 3T3-L1 preadipocytes and mesenchymal stem cells. Here, we investigate the functional roles of RPTP mu and the mechanism of its involvement in the regulation of signal transduction during adipogenesis of 3T3-L1 cells. Depletion of endogenous RPTP mu by RNA interference significantly inhibited adipogenic differentiation, whereas RPTP mu overexpression led to an increase in adipogenic differentiation. Ectopic expression of p120 catenin suppressed adipocyte differentiation, and the decrease in adipogenesis by p120 catenin was recovered by introducing RPTP mu. Moreover, RPTP mu induced a decrease in the cytoplasmic p120 catenin expression by reducing its tyrosine phosphorylation level, consequently leading to enhanced translocation of Glut-4 to the plasma membrane. On the basis of these results, we propose that RPTP mu acts as a positive regulator of adipogenesis by modulating the cytoplasmic p120 catenin level. Our data conclusively demonstrate that differentiation into adipocytes is controlled by RPTP mu, supporting the utility of RPTP mu and p120 catenin as novel target proteins for the treatment of obesity.