The role of Mitogen Activated Protein Kinase (MAPK) Phosphatases (MKPs) in adipogenesis : A study of Vaccinia H1-related (VHR) phosphatase

Abstract

Animals store most excess energy as fat in specialized cells called adipocytes which form the major part of adipose tissue. Since obesity, which has reached epidemic proportions in the last decades, is the result of excess growth of the adipose tissue caused by both hypertrophy and hyperplasia, understanding how adipocytes expand is an important area research. Adipogenesis, the development of progenitor cells to mature adipocytes, has been widely studied with mouse models and in particular with differentiation of the murine preadipocytes 3T3-L1 and 3T3-F22A. Previous research has found Mitogen Activated Protein kinase (MAPK) activity to be required in the early stages of adipogenesis. MKPs are phosphatases with MAPKs as their substrate. They are known to dephosphorylate MAPKs in several tissues. MKP1 has been shown to have a role in adipogenesis as it can regulate phosphorylation of the MAPK ERK in differentiating 3T3-L1 cells. Previous findings in our group have shown many MKPs to be regulated at the mRNA level during 3T3-L1 differentiation; one of these, MKP5, has been shown to enhance adipocyte differentiation when ectopically expressed. In this study we found that one of the other MKPs, Vaccinia H1-related (VHR) phosphatase is regulated during adipogenesis. We also validate the integrity of two kinds of expression vector constructs created for three MKPs (VHR, MKP6 and VH5) all of which have been shown to be regulated during adipogenesis. The vector constructs for VHR were used in characterization of its potential role in differentiation of 3T3-L1 cells. These results further underscore the importance of MKPs in adipogenesis and pave the way for future studies.