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Vanadate enhances leptin-induced activation of JAK/STAT pathway in CHO cells

2003; Elsevier BV; Volume: 302; Issue: 4 Linguagem: Inglês

10.1016/s0006-291x(03)00264-x

1090-2104

Atsushi Kita, Shigeo Uotani, Hironaga Kuwahara, Ryoko Takahashi, Katsuya Oshima, Hironori Yamasaki, Hiroyuki Mizuguchi, Takao Hayakawa, Yuji Nagayama, Yoshihiko Yamaguchi, Katsumi Eguchi,

Cytokine Signaling Pathways and Interactions

Leptin, the product of the ob gene, is an adipocyte-derived hormone that plays a key role in the control of food intake and energy expenditure. Leptin acts through receptors that belong to a member of the class I cytokine receptor family. It has been demonstrated that the SH2 domain-containing tyrosine phosphatase 2 (SHP-2) negatively regulates STAT3-mediated transcriptional activation through long form leptin receptor (OBRb). Vanadate has been shown to be a potent and selective inhibitor of PTPase activity in vitro. In this study, we have demonstrated that vanadate increases leptin-induced JAK2 and STAT3 phosphorylation in CHO cells expressing OBRb. The increased leptin-dependent luciferase activity of SOCS3 gene was also seen in vanadate-treated cell. Furthermore, vanadate reversed the inhibitory effects of SOCS3 on leptin-induced STAT3 phosphorylation. The present findings suggest that PTP inhibitors including vanadate and vanadate-derived compounds could be used as a therapeutic agent in the treatment of obesity.