ArticleThe Biochemical journal2002
Biphasic regulation of extracellular-signal-regulated protein kinase by leptin in macrophages: role in regulating STAT3 Ser727 phosphorylation and DNA binding.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 65 citations in OpenAlex.
- Differential effects of leptin on adiponectin expression with weight gain versus obesity.International journal of obesity (2005) · 2016Trial
- Sucrose solution, but not liquid sucrose diet, leads to leptin resistance irrespective of the time of day that sucrose is available.Physiology & behavior · 2023Article
- Luteolin Alters Macrophage Polarization to Inhibit Inflammation.Inflammation · 2020Article
- Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1.Cell death & disease · 2020Article
- Gene expression changes and promoter methylation with the combined effects of estradiol and leptin in uterine tissue of the ovariectomized mice model of menopause.Molecular biology reports · 2020Article
- Source of dietary sucrose influences development of leptin resistance in male and female rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- In vivo and in vitro evidence that chronic activation of the hexosamine biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- LIF-STAT signaling and trophoblast biology.JAK-STAT · 2013Review
- Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells.The Biochemical journal · 2013Article
- Signal transduction in cerebral arteries after subarachnoid hemorrhage-a phosphoproteomic approach.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Novel proteolytic microvesicles released from human macrophages after exposure to tobacco smoke.The American journal of pathology · 2013Article
- Leptin differentially regulate STAT3 activation in ob/ob mouse adipose mesenchymal stem cells.Nutrition & metabolism · 2012Article
- SOCS3 modulates interleukin-6R signaling preference in dermal fibroblasts.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2012Article
- Suppressor of cytokine signaling-2 gene disruption promotes Apc(Min/+) tumorigenesis and activator protein-1 activation.The American journal of pathology · 2010Article
- The Cdk5/p35 kinases modulate leptin-induced STAT3 signaling.Journal of molecular neuroscience : MN · 2009Article
- Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells.Cancer science · 2009Article
- Leptin signaling: A key pathway in immune responses.Current signal transduction therapy · 2009Article
- Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT and MAPK pathways.Endocrine · 2007Article
- Intracellular signalling pathways activated by leptin.The Biochemical journal · 2006Review
- Proline-, glutamic acid-, and leucine-rich protein-1 is essential in growth factor regulation of signal transducers and activators of transcription 3 activation.Cancer research · 2005Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) requires dimerization that is induced by phosphorylation of Tyr705, but its activity can be further modulated by phosphorylation at Ser727 in a manner that is dependent on cell context and the stimulus used. The role of STAT3 Ser727 phosphorylation in leptin signalling is currently not known. While cells transfected with the signalling-competent long form of the leptin receptor (ObRb) have been used to study leptin signalling, these are likely to be of limited use in studying STAT3 Ser727 phosphorylation due to the importance of cell background in determining the nature of the response. However, we have recently found that J774.2 macrophages endogenously express high levels of ObRb, and using these cells we find that leptin stimulates STAT3 phosphorylation on both Tyr705 and Ser727. The phosphorylation of Ser727 was not affected by rapamycin or the protein kinase C inhibitor H7 [1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride]. While the MEK-1 [mitogen-activated protein kinase (MAP kinase)/extracellular-signal-related kinase (ERK) kinase-1] inhibitor PD98059 [(2-amino-3'-methoxyphenyl)oxanaphthalen-4-one] had no effect on leptin-stimulated phosphorylation of STAT3 Tyr705, it greatly attenuated leptin's effects on STAT3 Ser727 phosphorylation. Further, Ob's effect on the DNA binding activity of STAT3 was also greatly reduced at all time points by PD98059. Leptin-induced ERK activation in J774.2 cells shows a biphasic pattern, with an initial reduction in ERK phosphorylation for up to 10 min following leptin stimulation, while at later time points phosphorylation of ERK was increased above basal levels. The increase in ERK activity corresponded with an increase in both phosphorylation of Ser727 and STAT3 DNA binding activity. These data provide the first evidence that ERK-mediated phosphorylation of Ser727 is required for full stimulation of STAT3 by leptin.
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