Protein-tyrosine Phosphatase-1B acts as a negative regulator of insulin signal transduction

Byon, John; Kusari, Anasua B.; Kusari, Jyotirmoy

doi:10.1007/978-1-4615-5647-3_11

Cited by 77 publications

(99 citation statements)

References 44 publications

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“…Recent studies indicate that PTP1B undergoes tyrosine phosphorylation after insulin stimulation and that this is positively correlated with enzyme activity (8,12). To determine the effect of development on PTP1B tyrosine phosphorylation, equal amounts of skeletal muscle and liver extracts were immunoprecipitated with anti-PY antibody followed by immunoblotting with anti-PTP1B antibody.…”

Section: Resultsmentioning

confidence: 99%

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Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

Suryawan

Davis

2003

American Journal of Physiology-Endocrinology and Metabolism

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Suryawan, Agus, and Teresa A. Davis. Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs. Am J Physiol Endocrinol Metab 284: E47-E54, 2003. First published September 11, 2002 10.1152/ajpendo.00210.2002The high activity of the insulin-signaling pathway contributes to the enhanced feeding-induced stimulation of translation initiation in skeletal muscle of neonatal pigs. Protein-tyrosine-phosphatase 1B (PTP1B) is a negative regulator of the tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1). The activity of PTP1B is determined mainly by its association with IR and Grb2. We examined the level of PTP1B activity, PTP1B protein abundance, PTP1B tyrosine phosphorylation, and the association of PTP1B with IR and Grb2 in skeletal muscle and liver of fasted and fed 7-and 26-day-old pigs. PTP1B activity in skeletal muscle was lower (P Ͻ 0.05) in 7-compared with 26-day-old pigs but in liver was similar in the two age groups. PTP1B abundances were similar in muscle but lower (P Ͻ 0.05) in liver of 7-compared with 26-day-old pigs. PTP1B tyrosine phosphorylation in muscle was lower (P Ͻ 0.05) in 7-than in 26-day-old pigs. The associations of PTP1B with IR and with Grb2 were lower (P Ͻ 0.05) at 7 than at 26 days of age in muscle, but there were no age effects in liver. Finally, in both age groups, fasting did not have any effect on these parameters. These results indicate that basal PTP1B activation is developmentally regulated in skeletal muscle of neonatal pigs, consistent with the developmental changes in the activation of the insulin-signaling pathway reported previously. Reduced PTP1B activation in neonatal muscle likely contributes to the enhanced insulin sensitivity of skeletal muscle in neonatal pigs.neonate; insulin signaling; insulin sensitivity; protein synthesis THE ENHANCED ACTIVATION of the insulin-signaling pathway leading to translation initiation in skeletal muscle of the neonate after food consumption has an important role in the enhanced responsiveness of muscle protein synthesis to feeding in the neonate (13,16,26,27,37). We have shown that the feeding-induced activation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and phosphatidylinositol 3-kinase (PI 3-kinase), as well as the abundance of the IR, is enhanced in skeletal muscle of the neonatal pig and decreases markedly with development. This developmental decline in the feeding-induced activation of early insulin-signaling components parallels the developmental decline in the feeding-induced activation of downstream signaling proteins, leading to the stimulation of protein synthesis in skeletal muscle and the developmental decrease in the ability of insulin to stimulate muscle protein synthesis. However, the molecular mechanism that regulates the developmental decline in the insulin sensitivity of skeletal muscle in neonatal pigs has not been elucidated.When insulin binds to its receptor, it induces autophosphorylation of the receptor on its ty...

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Section: Resultsmentioning

confidence: 99%

“…Several studies have demonstrated that a reduction in PTP1B activity correlates with an enhanced insulin sensitivity (8). For example, enhanced insulin sensitivity after weight loss is closely correlated with a reduction in the abundance of PTP1B (1).…”

Section: Discussionmentioning

confidence: 99%

Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

Suryawan

Davis

2003

American Journal of Physiology-Endocrinology and Metabolism

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“…57 Several studies demonstrated that changes in abundance and distribution of PTPases could impair insulin signal transduction, causing insulin resistance. 58 Aberrant insulin signaling, which leads to insulin resistance, hyperinsulinaemia and increased concentrations of endogenous estrogen and androgen, was linked to high breast cancer risk by clinical and experimental evidence. 59 The above mentioned functions confirmed the expression behavior of selected genes, in tumor samples of our study and in metanalysis results.…”

Section: Discussionmentioning

confidence: 99%

Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues

Cimino

Fuso

Sfiligoi

et al. 2008

Intl Journal of Cancer

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Gene expression profiles were studied by microarray analysis in 2 sets of archival breast cancer tissues from patients with distinct clinical outcome. Seventy-seven differentially expressed genes were identified when comparing 30 cases with relapse and 30 cases without relapse within 72 months from surgery. These genes had a specific ontological distribution and some of them have been linked to breast cancer in previous studies: AIB1, the two keratin genes KRT5 and KRT15, RAF1, WIF1 and MSH6. Seven out of 77 differentially expressed genes were selected and analyzed by qRT-PCR in 127 cases of breast cancer. The expression levels of 6 upregulated genes (CKMT1B, DDX21, PRKDC, PTPN1, SLPI, YWHAE) showed a significant association to both disease-free and overall survival. Multivariate analysis using the significant factors (i.e., estrogen receptor and lymph node status) as covariates confirmed the association with survival. There was no correlation between the expression level of these genes and other clinical parameters. In contrast, SERPINA3, the only downregulated gene examined, was not associated with survival, but correlated with steroid receptor status. An indirect validation of our genes was provided by calculating their association with survival in 3 publicly available microarray datasets. CKMT1B expression was an independent prognostic marker in all 3 datasets, whereas other genes confirmed their association with disease-free survival in at least 1 dataset. This work provides a novel set of genes that could be used as independent prognostic markers and potential drug targets for breast cancer. ' 2008 Wiley-Liss, Inc.Key words: breast cancer; gene expression; microarray analysis; prognosticThe heterogeneous nature of breast cancer reflects the complexity of the molecular alterations that underlie the development and progression of this disease and poses serious problems to clinical management, also due to the lack of reliable pathological or molecular markers.There are a number of major open questions, such as the evaluation of risk of distant metastasis in cases characterized by the presence of favorable indicators (negative axillary lymph nodes and/or positive estrogen receptors), the prediction of response to chemotherapy and/or antiestrogenic therapy and the prediction of metastases sites for high-risk cancers. Moreover, the principal molecular alterations leading to aggressive clinical behavior, representing potential therapeutic targets, still need to be identified in addition to the well-known factor ERBB2 and the estrogen receptor pathways.Molecular profiling using DNA microarrays have provided sound advancements in this field. The expression profile of gene clusters were useful in classifying breast tumors in biological subgroups with clinical relevance, 1 or in low-versus high-risk classes for relapse, 2-5 or to predict responsiveness to either hormonal-or chemo-therapy. 6,7 In a well-known study, van't Veer et al. addressed the risk of relapse in node-negative patients, 2 one of the most clinicall...

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“…Protein tyrosine phosphatase 1B (PTP1B) was demonstrated to negatively regulate the insulin pathway via inactivation of IR and IRS1 [14][15][16] . Recently, the leptin pathway was also found to be regulated by PTP1B, in which the neuronal PTP1B binds and dephosphorylates JAK2, which was downstream of the leptin receptor, and subsequently inhibited leptin signaling [17,18] .…”

Section: Introductionmentioning

confidence: 99%

A sesquiterpene quinone, dysidine, from the sponge Dysidea villosa, activates the insulin pathway through inhibition of PTPases

Zhang

Guo

et al. 2009

Acta Pharmacol Sin

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Aim:The sesquiterpene hydroquinones/quinones belong to one class of marine sponge metabolites, and they have received considerable attention due to their varied biological activities, including anti-tumor, anti-HIV, and anti-inflammatory action. In order to probe the potential anti-diabetic effect of the sesquiterpene hydroquinones/quinones, the effect of dysidine on the insulin pathway was studied. Methods: The promotion of glucose uptake by dysidine was studied in differentiated 3T3-L1 cells. The increase in membrane-located GLUT4 by dysidine was studied in CHO-K1/GLUT4 and 3T3-L1 cells by immuno-staining. The activation of the insulin signaling pathway by dysidine was probed by Western blotting. The inhibition of PTPases by dysidine was detected in vitro. Results: Dysidine, found in the Hainan sponge Dysidea villosa in the Chinese South Sea, effectively activated the insulin signaling pathway, greatly promoted glucose uptake in 3T3-L1 cells, and showed strong insulin-sensitizing activities. The potential targets of action for dysidine were probed, and the results indicated that dysidine exhibited its cellular effects through activation of the insulin pathway, possibly through the inhibition of protein tyrosine phosphatases, with more specific inhibition against protein tyrosine phosphatase 1B (PTP1B). Conclusion: Our findings are expected to expand understanding of the biological activities of sesquiterpene hydroquinones/quinones, and they show that dysidine could be a potential lead compound in the development of an alternative adjuvant in insulin therapy.

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Protein-tyrosine Phosphatase-1B acts as a negative regulator of insulin signal transduction

Cited by 77 publications

References 44 publications

Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues

A sesquiterpene quinone, dysidine, from the sponge Dysidea villosa, activates the insulin pathway through inhibition of PTPases

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