PTP1B Regulates Leptin Signal Transduction In Vivo

Zabolotny, Janice M.; Bence, Kendra K.; Stricker–Krongrad, Alain; Haj, Fawaz G.; Wang, Yongping; Minokoshi, Yasuhiko; Kim, Young–Bum; Elmquist, Joel K.; Tartaglia, Louis A.; Kahn, Barbara B.; Neel, Benjamin G.

doi:10.1016/s1534-5807(02)00148-x

Cited by 749 publications

(633 citation statements)

References 35 publications

Supporting

Mentioning

588

Contrasting

Unclassified

Order By: Relevance

“…This effect was mimicked by stimulation of PTP1B ϩ/ϩ and PTP1B Ϫ/Ϫ primary hepatocytes with TNF-␣ or IL-6 or transfection of murine or HuH-7 human liver cells with PTP1B siRNA, indicating that hepatocytes lacking this phosphatase are hypersensitive to cytokine-mediated signaling. Although leptin-induced phosphorylation of the Tyr705 residue of STAT3 is de-phosphorylated by PTP1B, 17 in this study we reported, for the first time to our knowledge, a new substrate for PTP1B, the Tyr185 residue of JNK. We excluded the possibility of indirect effects of PTP1B deficiency, such as the up-regulation of dual-specificity phosphatase-9 (MKP-4/DUSP-9), 41 because its expression in the liver does not differ between PTP1B ϩ/ϩ and PTP1B Ϫ/Ϫ mice (results not shown).…”

Section: Discussioncontrasting

confidence: 49%

“…Similarly, PTP1B reduced IL-6 -induced phosphorylation of Tyr705 residue of STAT3, a well-known substrate of this phosphatase. 17 …”

Section: Ptp1b Decreased Tnf-␣-induced Jnk Phosphorylation In Human Amentioning

confidence: 99%

“…More recently, dephosphorylation of the Tyr705 residue of STAT3 was elicited by PTP1B. 17 Finally, on completion of the repair process and restoration of liver mass, hepatocyte proliferation is inhibited, most likely through transforming growth factor (TGF) ␤ and activin signaling. 18 Extensive analysis of the PTP1B-deficient (PTP1B Ϫ/Ϫ ) mice has confirmed that the IR is a key physiological target of PTP1B.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Protein Tyrosine Phosphatase 1B (PTP1B) Deficiency Accelerates Hepatic Regeneration in Mice

Revuelta-Cervantes

Mayoral

Miranda

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Protein tyrosine phosphatase 1B (PTP1B) is a key regulator of metabolism and cell growth by its ability to dephosphorylate tyrosine kinase receptors and modulate the intensity of their signaling cascades. Because liver regeneration involves tyrosine phosphorylation-mediated signaling, we investigated the role of PTP1B in this process by performing partial hepatectomy in wild-type (PTP1B ؉/؉ ) and PTP1B-deficient (PTP1B ؊/؊ ) mice. The expression of PCNA and cyclins D1 and E (cell proliferation markers) was enhanced in PTP1B ؊/؊ regenerating livers, in parallel with 5=-bromo-2=-deoxyuridine incorporation. Phosphorylation of JNK1/2 and STAT3, early triggers of hepatic regeneration in response to TNF-␣ and IL-6, was accelerated in PTP1B ؊/؊ mice compared with PTP1B ؉/؉ mice. These phosphorylations were increased in PTP1B ؊/؊ hepatocytes or by silencing PTP1B in wild-type cells and decreased further after the addition of recombinant PTP1B. Enhanced EGFand HGF receptor-mediated signaling was observed in regenerating livers lacking PTP1B and in EGF-or HGF-stimulated PTP1B ؊/؊ hepatocytes. Moreover, PTP1B ؊/؊ mice displayed a more rapid increase in intrahepatic lipid accumulation than PTP1B ؉/؉ control mice. Late responses to partial hepatectomy revealed additional divergences because stress-mediated signaling was attenuated at 24 to 96 hours in PTP1B ؊/؊ mice compared with PTP1B ؉/؉ mice. Finally, PTP1B deficiency also improves hepatic regeneration in mice fed a high-fat diet. These results suggest that pharmacological inhibition of PTP1B would improve liver regeneration in patients with acute or chronic liver injury.

show abstract

Section: Discussioncontrasting

confidence: 49%

“…Similarly, PTP1B reduced IL-6 -induced phosphorylation of Tyr705 residue of STAT3, a well-known substrate of this phosphatase. 17 …”

Section: Ptp1b Decreased Tnf-␣-induced Jnk Phosphorylation In Human Amentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Protein Tyrosine Phosphatase 1B (PTP1B) Deficiency Accelerates Hepatic Regeneration in Mice

Revuelta-Cervantes

Mayoral

Miranda

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…2). Protein-tyrosine phosphatase 1B, a well-known inhibitor of insulin action, also terminates leptin signaling through inactivation of JAK2 (35). Leptin acting through LRb has also been demonstrated to regulate insulin receptor substrate 1 and 2, mitogen-activated protein kinase, extracellular-regulated kinase, Akt, and phosphatidylinositol 3-kinase in the hypothalamus, raising the possibility of cross-talk between leptin and insulin (36).…”

Section: Leptinmentioning

confidence: 99%

“…Other factors implicated in leptin resistance in the brain include reduction in leptin transport across the bloodbrain barrier, induction of protein tyrosine phosphatase 1B activity, and dysregulation of neuropeptides (3,35). Collectively, these abnormalities increase appetite and weight, albeit to a lesser degree than congenital leptin deficiency (4).…”

Section: Role Of Leptin In Famine and Feastmentioning

confidence: 99%

Brain Adipocytokine Action and Metabolic Regulation

et al. 2006

View full text Add to dashboard Cite

Adipose tissue secretes factors that control various physiological systems. The fall in leptin during fasting mediates hyperphagia and suppresses thermogenesis, thyroid and reproductive hormones, and immune system. On the other hand, rising leptin levels in the fed state stimulate fatty acid oxidation, decrease appetite, and limit weight gain. These divergent effects of leptin occur through neuronal circuits in the hypothalamus and other brain areas. Leptin also regulates the activities of enzymes involved in lipid metabolism, e.g., AMP-activated protein kinase and stearoyl-CoA desaturase-1, and also interacts with insulin signaling in the brain. Adiponectin enhances fatty acid oxidation and insulin sensitivity, in part by stimulating AMP-activated protein kinase phosphorylation and activity in liver and muscle. Moreover, adiponectin decreases body fat by increasing energy expenditure and lipid catabolism. These effects involve peripheral and possibly central mechanisms. Adipose tissue mediates interconversion of steroid hormones and secretes proinflammatory cytokines, vasoactive peptides, and coagulation and complement proteins. Understanding the actions of these "adipocytokines" will provide insight into the pathogenesis and treatment of obesity and related diseases. Diabetes 55 (Suppl. 2): S145-S154, 2006 ADIPOSE TISSUE

show abstract

Roles for Ghrelin in the Regulation of Appetite and Body Weight

Cummings

Shannon²

2003

Arch Surg

255

142

View full text Add to dashboard Cite

besity is a global epidemic that has proven daunting to prevent and treat. The prevalences of obesity (body mass index [BMI] Ͼ30) and morbid obesity (BMI Ͼ40) among American adults are about 30% and 5%, respectively. 1 Obesity is so strongly associated with medical comorbidities and mortality that it has begun to overtake infectious diseases as the most significant contributor to ill health worldwide. 2,3 Overweight persons are also frequently stigmatized and consequently suffer from low self-esteem. Their motivation to achieve and maintain weight loss is often Herculean. In 1 study of 47 patients who had durably lost 45 kg or more after bariatric surgery, 100% preferred to be deaf, dyslexic, diabetic, or have heart disease rather than be obese again; leg amputation and blindness were preferred by 91.5% and 89.4%, respectively. 4 The traditional treatment paradigm of diet, exercise, and medication generally achieves no more than a 5% to 10% reduction in body weight, 5,6 and recidivism after such weight loss exceeds 90% within 5 years. 7,8 This failure arises because a robust homeostatic system of body weight regulation compensates for weight loss with increased hunger and decreased energy expenditure. [9][10][11] The molecular mediators of these compensatory responses to weight loss are potential targets for antiobesity treatments. Ghrelin is a potent orexigenic (appetite-stimulating) peptide that seems to participate in the adaptive response to weight loss. Therefore, ghrelin holds promise as a target for both medical and surgical approaches to obesity.

show abstract

PTP1B Regulates Leptin Signal Transduction In Vivo

Cited by 749 publications

References 35 publications

Protein Tyrosine Phosphatase 1B (PTP1B) Deficiency Accelerates Hepatic Regeneration in Mice

Protein Tyrosine Phosphatase 1B (PTP1B) Deficiency Accelerates Hepatic Regeneration in Mice

Brain Adipocytokine Action and Metabolic Regulation

Roles for Ghrelin in the Regulation of Appetite and Body Weight

Contact Info

Product

Resources

About