Protein Kinase C (PKC) β Modulates Serine Phosphorylation of Insulin Receptor Substrate‐1 (IRS‐1)—Effect of Overexpression of PKCβ on Insulin Signal Transduction

2004 ◽  
Vol 30 (2) ◽  
pp. 287-299 ◽  
Author(s):  
Tatsuo Ishizuka ◽  
Kazuo Kajita ◽  
Yoshiyuki Natsume ◽  
Yasunori Kawai ◽  
Yoshinori Kanoh ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Serine Phosphorylation ◽  
Insulin Receptor Substrate ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Kinase C ◽  
Pkc Β

scholarly journals Interplay and Effects of Temporal Changes in the Phosphorylation State of Serine-302, -307, and -318 of Insulin Receptor Substrate-1 on Insulin Action in Skeletal Muscle Cells

2008 ◽  
Vol 22 (12) ◽  
pp. 2729-2740 ◽  
Author(s):  
Cora Weigert ◽  
Matthias Kron ◽  
Hubert Kalbacher ◽  
Ann Kathrin Pohl ◽  
Heike Runge ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Insulin Action ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Insulin Signal ◽  
Kinase C ◽  
Phosphorylation Pattern

Abstract Transduction of the insulin signal is mediated by multisite Tyr and Ser/Thr phosphorylation of the insulin receptor substrates (IRSs). Previous studies on the function of single-site phosphorylation, particularly phosphorylation of Ser-302, -307, and -318 of IRS-1, showed attenuating as well as enhancing effects on insulin action. In this study we investigated a possible cross talk of these opposedly acting serine residues in insulin-stimulated skeletal muscle cells by monitoring phosphorylation kinetics, and applying loss of function, gain of function, and combination mutants of IRS-1. The phosphorylation at Ser-302 was rapid and transient, followed first by Ser-318 phosphorylation and later by phosphorylation of Ser-307, which remained elevated for 120 min. Mutation of Ser-302 to alanine clearly reduced the subsequent protein kinase C-ζ-mediated Ser-318 phosphorylation. The Ser-307 phosphorylation was independent of Ser-302 and/or Ser-318 phosphorylation status. The functional consequences of these phosphorylation patterns were studied by the expression of IRS-1 mutants. The E302A307E318 mutant simulating the early phosphorylation pattern resulted in a significant increase in Akt and glycogen synthase kinase 3 phosphorylation. Furthermore, glucose uptake was enhanced. Because the down-regulation of the insulin signal was not affected, this phosphorylation pattern seems to be involved in the enhancement but not in the termination of the insulin signal. This enhancing effect was completely absent when Ser-302 was unphosphorylated and Ser-307 was phosphorylated as simulated by the A302E307E318 mutant. Phospho-Ser-318, sequentially phosphorylated at least by protein kinase C-ζ and a mammalian target of rapamycin/raptor-dependent kinase, was part of the positive as well as of the subsequent negative phosphorylation pattern. Thus we conclude that insulin stimulation temporally generates different phosphorylation statuses of the same residues that exert different functions in insulin signaling.

scholarly journals Shp2 Is Required for Protein Kinase C-dependent Phosphorylation of Serine 307 in Insulin Receptor Substrate-1

2005 ◽  
Vol 280 (38) ◽  
pp. 32693-32699 ◽  
Author(s):  
Karsten Müssig ◽  
Harald Staiger ◽  
Hendrik Fiedler ◽  
Klaus Moeschel ◽  
Alexander Beck ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Kinase C

scholarly journals The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1

2012 ◽  
Vol 2012 ◽  
pp. 1-8
Author(s):  
Christine Zhiwen Hu ◽  
Jaswinder K. Sethi ◽  
Thilo Hagen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Ubiquitin Ligases ◽  
Insulin Receptor Substrate ◽  
E3 Ubiquitin Ligases ◽  
Kinase C ◽  
Cullin 5 ◽  
Socs Proteins ◽  
Protein Kinase C Activation

Background. SOCS proteins are known to negatively regulate insulin signaling by inhibiting insulin receptor substrate-1 (IRS1). IRS1 has been reported to be a substrate for ubiquitin-dependent proteasomal degradation. Given that SOCS proteins can function as substrate receptor subunits of Cullin-5 E3 ubiquitin ligases, we examined whether Cullin-5 dependent ubiquitination is involved in the regulation of basal IRS1 protein stability and signal-induced IRS1 degradation.Findings. Our results indicate that basal IRS1 stability varies between cell types. However, the Cullin-5 E3 ligase does not play a major role in mediating IRS1 ubiquitination under basal conditions. Protein kinase C activation triggered pronounced IRS1 destabilization. However, this effect was also independent of the function of Cullin-5 E3 ubiquitin ligases.Conclusions. In conclusion, SOCS proteins do not exert a negative regulatory effect on IRS1 by functioning as substrate receptors for Cullin-5-based E3 ubiquitin ligases both under basal conditions and when IRS1 degradation is induced by protein kinase C activation.

scholarly journals Phosphorylation of Ser357of Rat Insulin Receptor Substrate-1 Mediates Adverse Effects of Protein Kinase C-δ on Insulin Action in Skeletal Muscle Cells

2008 ◽  
Vol 283 (17) ◽  
pp. 11226-11233 ◽  
Author(s):  
Rizwana Sanaullah Waraich ◽  
Cora Weigert ◽  
Hubert Kalbacher ◽  
Anita M. Hennige ◽  
Stefan Z. Lutz ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Adverse Effects ◽  
Insulin Receptor ◽  
Insulin Action ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Insulin Receptor Substrate ◽  
Kinase C
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