Specific inhibition by hGRB10ζ of insulin-induced glycogen synthase activation: evidence for a novel signaling pathway

Mounier, Cathérine; Lavoie, Louis; Dumas, Víctor; Mohammad-Ali, Khosro; Wu, Jiong; Nantel, André; Bergeron, John J.M.; Thomas, David Y.; Posner, Barry I.

doi:10.1016/s0303-7207(00)00439-1

Cited by 35 publications

(30 citation statements)

References 47 publications

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“…This is in agreement with experiments in which a human Grb10 isoform was overexpressed in rat hepatocytes, resulting in the specific inhibition of insulin-stimulated glycogen synthase (34). In addition, it lends support for previous in vitro data demonstrating an interaction between Grb10 and the insulin receptor (2)(3)(4).…”

Section: Discussionsupporting

confidence: 91%

Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism

Charalambous

Smith

Bennett

et al. 2003

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

260

275

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To investigate the function of the Grb10 adapter protein, we have generated mice in which the Grb10 gene was disrupted by a gene-trap insertion. Our experiments confirm that Grb10 is subject to genomic imprinting with the majority of Grb10 expression arising from the maternally inherited allele. Consistent with this, disruption of the maternal allele results in overgrowth of both the embryo and placenta such that mutant mice are at birth Ϸ30% larger than normal. This observation establishes that Grb10 is a potent growth inhibitor. In humans, GRB10 is located at chromosome 7p11.2-p12 and has been associated with Silver-Russell syndrome, in which Ϸ10% of those affected inherit both copies of chromosome 7 from their mother. Our results indicate that changes in GRB10 dosage could, in at least some cases, account for the severe growth retardation that is characteristic of Silver-Russell syndrome. Because Grb10 is a signaling protein capable of interacting with tyrosine kinase receptors, we tested genetically whether Grb10 might act downstream of insulin-like growth factor 2, a paternally expressed growth-promoting gene. The result indicates that Grb10 action is essentially independent of insulinlike growth factor 2, providing evidence that imprinting acts on at least two major fetal growth axes in a manner consistent with parent-offspring conflict theory.adapter protein ͉ cell signaling ͉ genomic imprinting ͉ growth factor receptor-bound protein ͉ insulin-like growth factor

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Section: Discussionsupporting

confidence: 91%

Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism

Charalambous

Smith

Bennett

et al. 2003

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

260

275

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“…In mouse embryonic fibroblast cell lines, IGF-I-mediated mitosis is inhibited by Grb10 (MORRIONE et al, 1997). In addition, Grb10 over-expression inhibits insulinstimulated glycogen synthesis in rat hepatocytes (MOUNIER et al, 2001). Taken together with the results of this study, we suggest that in bovine COCs Grb10 is probably involved in proliferative events controlling tyrosine kinase receptors activity.…”

Section: Discussionsupporting

confidence: 82%

Grb10 characterization in bovine cumulus oocyte complexes from different follicle sizes

et al. 2015

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“…In agreement with these studies, we have observed a Grb10-mediated decrease in phosphorylation of IR substrates, including IRS-1/2 (this study) (16), p62 dok (16,39), and Shc (data not shown). However, Mournier et al (21) reported that overexpression of hGrb10 did not affect IRS tyrosine phosphorylation, PI 3-kinase activity or Akt activity in rat hepatocytes, although IR kinase activity and IR autophosphorylation were reportedly reduced. Our results in CHO/IR cells show that the catalytic activity of the RTK toward itself is not significantly impaired by Grb10.…”

Section: Discussionmentioning

confidence: 96%

“…However, several studies indicate that Grb10 may regulate downstream events in various signaling pathways. Overexpression of hGrb10␥ (Grb10) in rat hepatocytes inhibits insulin-stimulated glycogen synthase activity, through a proposed novel pathway outside of the classical PI 3-kinase to Akt/glycogen synthase kinase-3 signaling (21). Grb10 has also been found to associate with tyrosine-phosphorylated c-kit receptor, and synergistically promote Akt activation.…”

mentioning

confidence: 99%

Grb10 Inhibits Insulin-stimulated Insulin Receptor Substrate (IRS)-Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Disrupting the Association of IRS-1/IRS-2 with the Insulin Receptor

Wick¹,

Werner

Langlais³

et al. 2003

Journal of Biological Chemistry

113

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Specific inhibition by hGRB10ζ of insulin-induced glycogen synthase activation: evidence for a novel signaling pathway

Cited by 35 publications

References 47 publications

Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism

Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism

Grb10 characterization in bovine cumulus oocyte complexes from different follicle sizes

Grb10 Inhibits Insulin-stimulated Insulin Receptor Substrate (IRS)-Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Disrupting the Association of IRS-1/IRS-2 with the Insulin Receptor

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