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

• Authors: Won Kon Kim, Hyeyun Jung, Eun Young Kim, Do Hyung Kim, Yee Sook Cho, Byoung Chul Park, Sung Goo Park, Yong Ko, Kwang-Hee Bae, Sang Chul Lee
• Journal: Molecular biology of the cell (Mol Biol Cell) Vol. 22 Issue 24 Pg. 4883-91 (Dec 2011) ISSN: 1939-4586 [Electronic] United States
• PMID: 21998202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catenins
• Glucose Transporter Type 4
• Slc2a4 protein, mouse
• Ptprm protein, mouse
• Receptor-Like Protein Tyrosine Phosphatases, Class 2
• Delta Catenin
• Ctnnd1 protein, mouse

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, metabolism)
• Adipogenesis (physiology)
• Animals
• Catenins (biosynthesis, genetics)
• Cell Differentiation (physiology)
• Cell Membrane (genetics, metabolism)
• Glucose Transporter Type 4 (genetics, metabolism)
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Phosphorylation (physiology)
• Protein Transport (physiology)
• RNA Interference
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (genetics, metabolism)
• Delta Catenin