Serine residues 994 and 1023/25 are important for insulin receptor kinase inhibition by protein kinase C isoforms β2 and θ

Strack, Volker; Hennige, Anita M.; Krützfeldt, Jan; Bossenmaier, Birgit; Klein, Harald; Kellerer, Monika; Lammers, Reiner; Häring, Hans‐Ulrich

doi:10.1007/s001250051327

Cited by 55 publications

(39 citation statements)

References 39 publications

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“…Serine phosphorylation sites have been mapped to several residues including S 307 , S 312 , and S 616 in human IRS-1 (23,(41)(42)(43); insulin resistance has been linked to serine phosphorylation of IRS-1. Our finding that BVR phosphorylates synthetic IRS-1 peptides specifically lacking tyrosine, but otherwise identical to IRS-1 peptides used as IRK substrates, indicates that IRS-1 is a likely substrate for BVR serine͞threonine kinase activity.…”

Section: Discussionmentioning

confidence: 99%

Human biliverdin reductase: A member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity

Lerner-Marmarosh

Shen

Torno

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

132

222

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Section: Discussionmentioning

confidence: 99%

Human biliverdin reductase: A member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity

Lerner-Marmarosh

Shen

Torno

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

132

222

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“…It is possible that activated PKC isoform(s) impairs insulin signalling by increasing the phosphorylation of insulin receptor susbtrates (IRS)-1/2 at serine/threonine residues. Indeed, PKC isoform(s) attenuates insulin signalling by IRS-1 phosphorylation at serine/threonine residues (Chin et al 1994, Bossenmaier et al 1997, De Fea & Roth 1997, Strack et al 2000. Therefore, activation of PKC isoform(s) might be an important negative regulator of insulin receptor function.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells

Hsieh¹,

Fustier²,

Wei³

et al. 2004

Journal of Endocrinology

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We reported previously that insulin inhibits the stimulatory effect of high glucose on the expression of angiotensinogen (ANG) gene in both rat immortalized renal proximal tubular cells (IRPTCs) and non-diabetic rat renal proximal tubular cells (RPTCs), but has no effect in diabetic rat RPTCs. In the present study we investigated whether hyperglycaemia-induced resistance to the insulininduced inhibition of expression of the ANG gene is mediated via the generation of reactive oxygen species (ROS) in RPTCs. Rat IRPTCs were cultured for 2 weeks in high-glucose (25 mM) or normal-glucose (5 mM) medium plus angiotensin II (Ang II) with or without a superoxide scavenger (tiron), or inhibitors of: NADPH oxidase (diphenylene iodinium, DPI), Ang II type 1 and 2 receptors (losartan and PD123319), angiotensinconverting enzyme (perindopril), protein kinase C (GF 109203X), or glutamine:fructose-6-phosphate aminotransferase (azaserine). Cellular generation of ROS, and ANG and renin mRNA levels were assessed by lucigenin assay and specific reverse transcriptase-PCR respectively. Phosphorylation of p44/42 mitogen-activated protein kinase (p44/42 MAPK) was evaluated by western blotting. Prolonged exposure of IRPTCs to high concentrations of glucose or Ang II evoked generation of ROS and resistance to the insulin-induced inhibition of expression of the ANG gene and of p44/42 MAPK phosphorylation. Co-incubation of IRPTCs with tiron, DPI, losartan, PD123319, perindopril, GF 109203X or azaserine prevented ROS generation, restoring the inhibitory action of insulin on ANG gene expression and on p44/42 MAPK phosphorylation. In conclusion, our studies demonstrate that blockade of both ROS generation and activation of the intrarenal renin-angiotensin system improves the inhibitory action of insulin on ANG gene expression in IRPTCs in conditions of high glucose.

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“…As a serine-threonine kinase, PKCδ might be expected to function primarily as a negative regulator of IR signaling, particularly in view of the role of serine phosphorylation on activities of IR and IRS [103][104][105]. And, indeed, many studies have shown that activated PKCδ readily serine phosphorylates these important proteins.…”

Section: Novel Pkc Isoforms Pkcδmentioning

confidence: 99%

Specific protein kinase C isoforms as transducers and modulators of insulin signaling

Sampson

Cooper

2006

Molecular Genetics and Metabolism

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Recent studies implicate specific PKC isoforms in the insulin-signaling cascade. Insulin activates PKCsα, βII, δ and ζ in several cell types. In addition, as will be documented in this review, certain members of the PKC family may also be activated and act upstream of PI3 and MAP kinases. Each of these isoforms has been shown one way or another either to mimic or to modify insulin-stimulated effects in one or all of the insulin-responsive tissues. Moreover, each of the isoforms has been shown to be activated by insulin stimulation or conditions important for effective insulin stimulation. Studies attempting to demonstrate a definitive role for any of the isoforms have been performed on different cells, ranging from appropriate model systems for skeletal muscle, liver and fat, such as primary cultures, and cell lines and even in vivo studies, including transgenic mice with selective deletion of specific PKC isoforms. In addition, studies have been done on certain expression systems such as CHO or HEK293 cells, which are far removed from the tissues themselves and serve mainly as vessels for potential protein-protein interactions. Thus, a clear picture for many of the isoforms remains elusive in spite of over two decades of intensive research. The recent intrusion of transgenic and precise molecular biology technologies into the research armamentarium has opened a wide range of additional possibilities for direct involvement of individual isoforms in the insulin signaling cascade. As we hope to discuss within the context of this review, whereas many of the long soughtafter answers to specific questions are not yet clear, major advances have been made in our understanding of precise roles for individual PKC isoforms in mediation of insulin effects. In this review, in which we shall focus our attention on isoforms in the conventional and novel categories, a clear case will be made to show that these isoforms are not only expressed but are importantly involved in regulation of insulin metabolic effects.

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Serine residues 994 and 1023/25 are important for insulin receptor kinase inhibition by protein kinase C isoforms β2 and θ

Cited by 55 publications

References 39 publications

Human biliverdin reductase: A member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity

Human biliverdin reductase: A member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity

Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells

Specific protein kinase C isoforms as transducers and modulators of insulin signaling

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