Disease relevance of Ptpn1

• These results indicate that PTP1B may regulate gene expression of SREBP-1 via enhancement of PP2A activity, thus mediating hepatic lipogenesis and postprandial hypertriglyceridemia [1].
• Surprisingly, protein tyrosine phosphatase-1B association with insulin receptor was also increased by undernutrition [2].
• Lung air volume at 30 cm H2O Ptp (MLV30) showed a significantly higher linear relationship with body weight (r = 0.93) than with lung-heart weight (r = 0.80) as the independent variable [3].
• The hydroxyl radical scavenger dimethylsulfoxide abolished the increase in Ptp and attenuated the increase in Ppa, but did not consistently protect the lungs from edema development [4].

High impact information on Ptpn1

• Here we demonstrate that WT-, but not PA-PTP1B, inhibits transformation of rat 3Y1 fibroblasts by v-crk, -src, and -ras, but not by v-raf [5].
• Expression of wild-type PTP1B (WT-PTP1B), but not a catalytically competent, proline-to-alanine point mutant that cannot bind p130Cas (PA-PTP1B), causes substantial tyrosine dephosphorylation of p130Cas (F. Liu, D. E. Hill, and J. Chernoff, J. Biol. Chem. 271:31290-31295, 1996) [5].
• We have recently shown that protein tyrosine phosphatase 1B (PTP1B) associates with the docking protein p130Cas in 3Y1 rat fibroblasts [5].
• This interaction is mediated by a proline-rich sequence on PTP1B and the SH3 domain on p130Cas [5].
• Inhibition of protein tyrosine phosphatase 1B abrogated cAMP-mediated disruption of actin cytoskeleton, cav-1 phosphorylation, and FAK Tyr-397 dephosphorylation [6].

Biological context of Ptpn1

• Protein-tyrosine phosphatase 1B as new activator for hepatic lipogenesis via sterol regulatory element-binding protein-1 gene expression [1].
• These results show that PTP1B, best known as a negative regulator of the metabolic effects of insulin, is required for the effects of insulin on actin organization in immortalized fibroblasts [7].
• However, pretreatment with the PTP1B inhibitor resulted in a marked improvement in leptin-dependent suppression of food intake (P < 0.05) [8].
• In contrast, RSG did not affect the increased PTP1B levels and activities or the already reduced insulin-stimulated glycogen synthesis and tyrosine phosphorylation of IRbeta-subunits and IRS-2 in livers of diabetic rats [9].
• PTP1B has been shown to be a negative regulator of the insulin signal transduction in insulin resistant states [10].

Anatomical context of Ptpn1

• Protein-tyrosine phosphatase 1B mediates the effects of insulin on the actin cytoskeleton in immortalized fibroblasts [7].
• Diabetic rats showed significantly increased levels and activities of PTP1B in the skeletal muscle (1.6- and 2-fold, respectively) and liver (1.7- and 1.8-fold, respectively), thus diminishing insulin signaling in the target tissues [9].
• In 28-week-old-MSG rats there was an increase in IR/PTP1B interaction and reduced insulin signaling in liver, muscle and adipocytes, and a more pronounced insulin resistance [10].
• Immunoblotting of four candidate IR-PTPs demonstrated no change in PTP1B or the SH2 domain containing phosphatase-2 (SHP-2), whereas a significant decrease in leukocyte antigen-related phosphatase (LAR) (51 +/- 3% of control) and an increase in PTP-alpha (165 +/- 16%) were found [11].
• Stimulation of the alveolar macrophage respiratory burst by ADP causes selective glutathionylation of protein tyrosine phosphatase 1B [12].

Associations of Ptpn1 with chemical compounds

• We found that insulin-resistant rats fed a diet high in fructose showed an increased proteintyrosine phosphatase 1B (PTP1B) content with strong expression of SREBP-1 mRNA in the liver [1].
• Here we examine the role of PTP1B in the insulin-sensitizing action of rosiglitazone (RSG) in skeletal muscle and liver [9].
• Rosiglitazone ameliorates abnormal expression and activity of protein tyrosine phosphatase 1B in the skeletal muscle of fat-fed, streptozotocin-treated diabetic rats [9].
• Our results demonstrated that the increase in PTP1B expression and/or association with IR in MSG animals may contribute to the impaired insulin signaling mainly in liver and muscle [10].
• The distribution of PTP-1B in the light microsomes from resting adipocytes was similar to that of IRS-1 as determined by sucrose velocity gradient fractionation [13].

Enzymatic interactions of Ptpn1

• Analysis of the catalytic activity of partially purified rat adipocyte PTP-alpha and LAR and recombinant PTP-1B showed that all three PTPases dephosphorylate IR [13].

Regulatory relationships of Ptpn1

• Here we show that protein-tyrosine phosphatase 1B (PTPIB) activates Src, thereby initiating the activation of a Rac-dependent pathway leading to cytoskeletal remodeling [7].

Other interactions of Ptpn1

• Protein tyrosine phosphatase 1B (PTP1B) acts as a physiological negative regulator of insulin signaling by dephosphorylating the activated insulin receptor (IR) [9].
• SHP2 (P < 0.03) and PTP1B (P < 0.03) increased only in SM/SP with no change in PTEN in CM/SP and SM/SP groups [14].
• RSG treatment in normal rats did not significantly change PTP1B activities and levels or protein levels of IRbeta, IRS-1, and -2 in diabetic rats [9].
• Rat fibroblasts lacking PTP1B expression do not activate Src or Rac in response to insulin and cannot reorganize actin [7].
• PTP1B glutathionylation was dependent on H(2)O(2) as the presence of catalase at the time of ADP stimulation inhibited the formation of the conjugate [12].

Analytical, diagnostic and therapeutic context of Ptpn1

• PTP1B protein levels, as determined by Western blot, were significantly higher in mediobasal hypothalamic punches collected from 20-wk-old rats, compared with 8-wk-old rats (P < 0.05) [8].
• There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS [15].
• Quantitative PCR analysis showed that PTP1B and PTPL1 were induced approximately 30-fold and approximately 60-fold, respectively, by 2 weeks after injury in the damaged vessels compared with the uninjured vessels [16].
• The purpose of this study was to investigate the effect of changes in transpulmonary pressure (Ptp) and induced constriction on parenchymal bulk (k) and shear (mu) moduli [17].
• With increasing body size, the transpleural hydraulic pressure gradient (Ptp = Pepl - Pliq) at the level of the right atrium increased from 1.45 to 5.6 cmH2O going from rats to sheep [18].

References