RPTP? 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? (RPTP?) expression is markedly increased during the adipogenic differentiation of 3T3-L1 preadipocytes and mesenchymal stem cells. Here, we investigate the functional roles of RPTP? and the mechanism of its involvement in the regulation of signal transduction during adipogenesis of 3T3-L1 cells. Depletion of endogenous RPTP? by RNA interference significantly inhibited adipogenic differentiation, whereas RPTP? 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?. Moreover, RPTP? 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? 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?, supporting the utility of RPTP? and p120 catenin as novel target proteins for the treatment of obesity.

SUBMITTER: Kim WK 

PROVIDER: S-EPMC3237630 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature