scholarly journals The Differentiation of Skeletal Muscle Cells Involves a Protein-tyrosine Phosphatase-α-mediated C-Src Signaling Pathway

2002 ◽  
Vol 277 (48) ◽  
pp. 46687-46695 ◽  
Author(s):  
Huogen Lu ◽  
Poonam Shah ◽  
David Ennis ◽  
Gail Shinder ◽  
Jan Sap ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Protein Tyrosine ◽  
Src Signaling

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

2003 ◽  
Vol 284 (1) ◽  
pp. E47-E54 ◽  
Author(s):  
Agus Suryawan ◽  
Teresa A. Davis
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Tyrosine Phosphorylation ◽  
Insulin Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Age Groups ◽  
Protein Tyrosine Phosphatase 1B ◽  
Neonatal Pigs

The 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 < 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 < 0.05) in liver of 7- compared with 26-day-old pigs. PTP1B tyrosine phosphorylation in muscle was lower (P < 0.05) in 7- than in 26-day-old pigs. The associations of PTP1B with IR and with Grb2 were lower (P < 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.

scholarly journals Inhibition of the Protein Tyrosine Phosphatase SHP-1 Increases Glucose Uptake in Skeletal Muscle Cells by Augmenting Insulin Receptor Signaling and GLUT4 Expression

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4581-4588 ◽  
Author(s):  
Sébastien Bergeron ◽  
Marie-Julie Dubois ◽  
Kerstin Bellmann ◽  
Michael Schwab ◽  
Nancy Larochelle ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Protein Tyrosine Phosphatase ◽  
Insulin Action ◽  
Tyrosine Phosphatase ◽  
Glycogen Synthesis ◽  
Glut4 Translocation ◽  
Protein Tyrosine ◽  
Glut4 Expression

The protein tyrosine phosphatase (PTPase) Src-homology 2-domain-containing phosphatase (SHP)-1 was recently reported to be a novel regulator of insulin's metabolic action. In order to examine the role of this PTPase in skeletal muscle, we used adenovirus (AdV)-mediated gene transfer to express an interfering mutant of SHP-1 [dominant negative (DN)SHP-1; mutation C453S] in L6 myocytes. Expression of DNSHP-1 increased insulin-induced Akt serine-threonine kinase phosphorylation and augmented glucose uptake and glycogen synthesis. Pharmacological inhibition of glucose transporter type 4 (GLUT4) activity using indinavir and GLUT4 translocation assays revealed an important role for this transporter in the increased insulin-induced glucose uptake in DNSHP-1-expressing myocytes. Both GLUT4 mRNA and protein expression were also found to be increased by DNSHP-1 expression. Furthermore, AdV-mediated delivery of DNSHP-1 in skeletal muscle of transgenic mice overexpressing Coxsackie and AdV receptor also enhanced GLUT4 protein expression. Together, these findings confirm that SHP-1 regulates muscle insulin action in a cell-autonomous manner and further suggest that the PTPase negatively modulates insulin action through down-regulation of both insulin signaling to Akt and GLUT4 translocation, as well as GLUT4 expression.

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