Vanadate enhances leptin-induced activation of JAK/STAT pathway in CHO cells.
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.
Kita
Atsushi
A
First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Uotani
Shigeo
S
Kuwahara
Hironaga
H
Takahashi
Ryoko
R
Oshima
Katsuya
K
Yamasaki
Hironori
H
Mizuguchi
Hiroyuki
H
Hayakawa
Takao
T
Nagayama
Yuji
Y
Yamaguchi
Yoshihiko
Y
Eguchi
Katsumi
K
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D017930:Genes, Reporter; D006801:Humans; D053614:Janus Kinase 2; D020738:Leptin / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014638:Vanadates / Q000378:metabolism*; D018909:src Homology Domains
D004268:DNA-Binding Proteins; C515448:LEPR protein, human; D020738:Leptin; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2