English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Serine phosphorylation of the insulin receptor (IR) has been proposed to exert an inhibitory influence on its tyrosine kinase activity. Previous works using site-directed mutagenesis suggested that serine 994 of the IR (IR Ser 994) might be part of an inhibitory domain of the receptor. In this study we examined whether this residue is subjected to phosphorylation in vivo. We used a site-phosphospecific antibody to determine the extent of phosphorylation of IR Ser 994 in insulin target tissues from two animal models of insulin resistance with different IR kinase (IRK) activity: obese (fa/fa) Zucker rats and transgenic mice overexpressing bovine growth hormone (PEPCK-bGH mice). Phosphorylation at IR Ser 994 was markedly increased in liver of obese rats. This alteration appeared to be tissue-selective since no phosphorylation on Ser 994 was detected in IRs isolated from skeletal muscle of these animals. On the other hand, the phosphorylation level of IR Ser 994 was very low in liver of PEPCK-bGH mice and did not differ from that of the control group. We have also demonstrated that protein kinase (PK) C isoforms alpha, betaI and zeta are able to promote the in vitro phosphorylation of the IR on Ser 994. Differential findings in these two models of insulin resistance might thus reflect increased PKC activity resulting from increased lipid availability in obese Zucker rats. Our results suggest that Ser 994 is a novel in vivo IR phosphorylation site that might be involved in the regulation of the IRK in some states of insulin resistance.

Increased in vivo phosphorylation of insulin receptor at serine 994 in the liver of obese insulin-resistant Zucker rats