scholarly journals Phosphoinositide 3-Kinase-mediated Reduction of Insulin Receptor Substrate-1/2 Protein Expression via Different Mechanisms Contributes to the Insulin-induced Desensitization of Its Signaling Pathways in L6 Muscle Cells

2003 ◽  
Vol 278 (18) ◽  
pp. 15641-15651 ◽  
Author(s):  
Luciano Pirola ◽  
Stephanie Bonnafous ◽  
Anne M. Johnston ◽  
Claire Chaussade ◽  
Fiorella Portis ◽  
...  
Keyword(s):  
Protein Expression ◽  
Insulin Receptor ◽  
Signaling Pathways ◽  
Muscle Cells ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Phosphoinositide 3 Kinase ◽  
L6 Muscle Cells ◽  
Mediated Reduction

Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3-kinase signaling in muscle cells: consequences on proteolysis

2004 ◽  
Vol 287 (4) ◽  
pp. F700-F706 ◽  
Author(s):  
Harold A. Franch ◽  
Sina Raissi ◽  
Xiaonan Wang ◽  
Bin Zheng ◽  
James L. Bailey ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Protein Degradation ◽  
Insulin Signaling ◽  
Muscle Cells ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Pi3k Activity ◽  
Tnf Α ◽  
Phosphoinositide 3 Kinase ◽  
In Cells

Chronic acidosis is a stimulus for proteolysis in muscle in vivo, but the mechanism of this response is unknown. We tested the hypothesis that acidosis or TNF-α, a cytokine whose production increases in acidosis, regulates proteolysis by inhibiting insulin signaling through phosphoinositide 3-kinase (PI3K). In cultured L6 myotubes, acidified (pH 7.1) media did not accelerate the basal protein degradation rate, but it inhibited insulin’s ability to suppress proteolysis. Insulin receptor substrate-1 (IRS-1)-associated PI3K activity was not altered in cells acidified for 10 min but was strongly inhibited in cells incubated at pH 7.1 for 24 h. Phosphorylation of Akt was also suppressed by acidification for 24 h. Acidification did not induce changes in IRS-1 abundance, insulin-stimulated IRS-1 tyrosine phosphorylation, or the amount of PI3K p85 regulatory subunit. In contrast to acidification, TNF-α suppressed proteolysis in the presence or absence of insulin but had no effect on IRS-1-associated PI3K activity. To establish that the PI3K pathway can regulate protein degradation in muscle, we measured proteolysis in cells after inhibition of PI3K activity with LY-294002 or infection with an adenovirus encoding a dominant negative PI3K p85α-subunit. Both approaches inhibited insulin-induced suppression of proteolysis to a degree similar to that seen with acidification. We conclude that acidosis accelerates protein degradation by impairing insulin signaling through PI3K in muscle cells.

scholarly journals Crk protein binds to PDGF receptor and insulin receptor substrate-1 with different modulating effects on PDGF- and insulin-dependent signaling pathways

Oncogene ◽  
1998 ◽  
Vol 16 (19) ◽  
pp. 2425-2434 ◽  
Author(s):  
Andrey Sorokin ◽  
Eleanor Reed ◽  
Naenna Nnkemere ◽  
Nickolai O Dulin ◽  
Joseph Schlessinger
Keyword(s):  
Insulin Receptor ◽  
Signaling Pathways ◽  
Insulin Receptor Substrate ◽  
Pdgf Receptor ◽  
Insulin Receptor Substrate 1 ◽  
Insulin Dependent

scholarly journals Reconstitution of Insulin Signaling Pathways in Rat 3Y1 Cells Lacking Insulin Receptor and Insulin Receptor Substrate-1

1998 ◽  
Vol 273 (39) ◽  
pp. 25347-25355 ◽  
Author(s):  
Takanobu Imanaka ◽  
Hideki Hayashi ◽  
Kazuhiro Kishi ◽  
Lihong Wang ◽  
Kazuo Ishii ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1
Sign in / Sign up

Export Citation Format

Share Document