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

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

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

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

Biochem Biophys Res Commun. 2003 Mar 21;302(4):805-9. doi: 10.1016/s0006-291x(03)00264-x.

Authors

Atsushi Kita¹, Shigeo Uotani, Hironaga Kuwahara, Ryoko Takahashi, Katsuya Oshima, Hironori Yamasaki, Hiroyuki Mizuguchi, Takao Hayakawa, Yuji Nagayama, Yoshihiko Yamaguchi, Katsumi Eguchi

Affiliation

¹ First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

PMID: 12646241
DOI: 10.1016/s0006-291x(03)00264-x

Abstract

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.

MeSH terms

Animals
CHO Cells
Cricetinae
DNA-Binding Proteins / metabolism*
Enzyme Activation
Genes, Reporter
Humans
Janus Kinase 2
Leptin / metabolism*
Phosphorylation
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / metabolism*
Proteins / genetics
Proteins / metabolism
Proto-Oncogene Proteins*
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
Receptors, Leptin
Repressor Proteins*
STAT3 Transcription Factor
Signal Transduction / physiology*
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Time Factors
Trans-Activators / metabolism*
Transcription Factors*
Vanadates / metabolism*
src Homology Domains

Substances

DNA-Binding Proteins
LEPR protein, human
Leptin
Proteins
Proto-Oncogene Proteins
Receptors, Cell Surface
Receptors, Leptin
Repressor Proteins
SOCS3 protein, human
STAT3 Transcription Factor
STAT3 protein, human
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Trans-Activators
Transcription Factors
Vanadates
Protein-Tyrosine Kinases
JAK2 protein, human
Janus Kinase 2