Recombinant Mouse Insulin receptor substrate 2 (Irs2), partial

1. Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4-indeuced M2a-subtype macrophage activation in obesity. PMID: 30451856
2. 'selective insulin resistance' is caused by the differential expression of Irs1 and Irs2 in different zones of the liver PMID: 27708333
3. Lung-specific dual ablation of insulin receptor substrates 1/2 (succumb to tumor burdenIrs1/Irs2) strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with Kras activation and p53 loss. Mice with Irs1/Irs2 loss eventually. PMID: 29610318
4. Insulin receptor substrate 2 (IRS2) is phosphorylated during induction of CAFLTP, a process that requires cytosolic free Ca2+. PMID: 27457910
5. diabetes in IRS2-deficient male mice is associated with increased oxidative stress and apoptosis in the hypothalamus. PMID: 27013528
6. identified a critical inhibitory loop downstream of IRS2, demonstrating an unanticipated and previously unrecognized role for IRS2 in suppressing allergic lung inflammation and remodeling. PMID: 27330190
7. possible link between impaired insulin sensing by NGNs and hyperphagic obese phenotype in IRS2 knockout mice PMID: 23840624
8. Mutation of five "inhibitory" Ser phosphorylation sites on IRS2 in transgenic mice that overexpress, selectively in pancreatic beta-cells, either wild-type (WT) or a mutated IRS2 protein (IRS2(5A)) led to increased islets size, number, and mRNA levels of catalase and superoxide dismutase, and decreased nitric oxide synthase in 7- to 10-week-old IRS2(5A)-beta mice compared with IRS2(WT)-beta mice. PMID: 28424159
9. data identify SH2B1 as a major regulator of IRS2 stability, demonstrate a novel feedback mechanism linking mTORC1 signaling with IRS2, and identify 4E-BP2 as a major regulator of proliferation and survival of beta-cells. PMID: 27217487
10. Decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice. PMID: 28190325
11. Acute knockdown of Insr or both Irs1 and Irs2 in adipocytes increased Adipoq mRNA expression but reduced adiponectin secretion. PMID: 26888756
12. Combination of DPP-4 inhibitor and PPARgamma agonist exerts protective effects on pancreatic beta-cells in diabetic db/db mice through the augmentation of IRS-2 expression PMID: 26116826
13. discovered that Irs2 deficiency causes insulin resistance through up-regulation of the phosphatase and tensin homolog (PTEN). Importantly, suppressing PTEN in Irs2(-/-) podocytes rescued insulin sensitivity PMID: 26384875
14. A knockout mouse has confirmed the importance of IRS2 in the control of glucose homeostasis and especially in the survival and function of pancreatic beta-cells. PMID: 24977713
15. The data suggest that Irs2 deletion in endothelial cells leads to a decreased islet blood flow, which may cause impaired glucose-induced insulin secretion. PMID: 25277391
16. Results indicate that although IRS isoforms (irs1 and irs2) play divergent roles in the developmental regulation of cardiac size, these isoforms exhibit nonredundant roles in mediating the hypertrophic and metabolic response of the heart to exercise. PMID: 25002528
17. Inhibition of Gsk-3beta by Irs-2-dependent PI3K signaling promotes glucose uptake and aerobic glycolysis. PMID: 24811175
18. Data (including data from knockout mice) suggest that Irs2 is not required for islet beta-cell proliferation (as seen with high-fat diet) but may be needed for beta-cell regeneration (as seen after partial pancreatectomy). PMID: 24517226
19. IRS2 plays a critical role in testicular development, potentially by mediating IGF1 signaling during embryonic and early postnatal development. PMID: 23741292
20. Mice with combined cardiomyocyte-specific deletion of Irs1 & Irs2 had unrestrained autophagy in cardiomyocytes, leading to myocyte loss, heart failure, premature death, apoptosis & mitochondrial dysfunction. PMID: 24177427
21. results demonstrate an unsuspected intersection between Hif-2alpha-mediated hypoxic signaling and hepatic insulin action through Irs2 induction, which can be co-opted by Vegf inhibitors to modulate glucose metabolism PMID: 24037094
22. AngII induced serine phosphorylation and tyrosine phosphorylation in IRS2 via PKC-Beta activation. PMID: 23775122
23. IRS2 protein degradation was dependent on the interaction with 14-3-3 proteins and the presence of serine 1137/1138. PMID: 23615913
24. CaMK4 regulates beta-cell proliferation and apoptosis in a CREB-dependent manner and CaMK4-induced IRS-2 expression is important in these processes PMID: 23049845
25. Decreased IRS2 expression and increased Bax expression may play an important role in the glucotoxicity in mouse islet cells. PMID: 19620044
26. we report that complete disruption of insulin receptor substrate 2 (Irs2) in mice impairs long-term potentiation (LTP) of synaptic transmission in the hippocampus PMID: 21955917
27. Deletion of Foxo1 from LepR-b neurons in Lepr(DeltaIrs2) mice normalized energy balance. PMID: 22560222
28. This study demonstrates for the first time a unique tissue-specific role of IRS2 in cochlear development and hearing function PMID: 22160220
29. Brain deletion of insulin receptor substrate 2 disrupts hippocampal synaptic plasticity and metaplasticity PMID: 22383997
30. Data indicate that IRS2 signalling is required for the proper development of spinal sensory neurons involved in the perception of pain. PMID: 22288475
31. A large proportion of the liver-related preautonomic dorsal motor nucleus and paraventricular hypothalamic neurons expresses IRS2. PMID: 21620379
32. dipeptidyl peptidase-4 inhibitor vildagliptin has an effect on glucose tolerance and beta-cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet PMID: 22315446
33. these data indicated that IRS-2 deficiency in macrophages enhanced their accumulation in the vascular wall accompanied by increased expression of proinflammatory mediators in macrophages. PMID: 22074825
34. Data suggest that glucose-induced (i.e., hyperglycemia) transcriptional control of IRS-2 gene expression in pancreatic islets is mediated by Ca2+/calcineurin/NFAT signaling pathway. PMID: 21940781
35. Increasing Irs2 levels in the brains of the R6/2 model of Huntington disease significantly reduced life span and increased neuronal oxidative stress and mitochondrial dysfunction. PMID: 21926467
36. Dorsal root ganglia neurons express insulin receptor substrate 2 that is altered by diabetes, and insulin signaling downstream of the insulin receptors may be impaired in sensory neurons and contribute to diabetic neuropathy. PMID: 21754917
37. Inducible nitric-oxide synthase and nitric oxide donor decrease insulin receptor substrate-2 protein expression by promoting proteasome-dependent degradation in pancreatic beta-cells: involvement of glycogen synthase kinase-3beta. PMID: 21700708
38. activation of the IGF-1R may directly regulate expression of IRS-1/2 during alveolar development and differentiation. PMID: 21628386
39. this study suggested that Irs2 is a negative regulator of memory formation as both NesCreIrs2KO and D6CreIrs2KO mice have enhanced memory. PMID: 21597043
40. oncogenic transformation by v-src in mouse embryonic fibroblasts requires the association of v-src with IRS-2; IRS-2 binds src through two tyrosine residues that also bind PI3-K PMID: 21532614
41. Results suggest that the Ca(2+)/CaMK(IV)/CREB cascade plays a critical role in the regulation of Irs2 expression in beta cells. PMID: 21301804
42. Leptin-stimulated activation of hypothalamic JAK2 and phosphorylation of hyphothalamic IRS2 were significantly impaired in SH2B1(-/-) mice. PMID: 20360640
43. Igf1r signals primarily through Irs1 and affects insulin secretion, whereas beta cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. PMID: 20947509
44. These findings suggest that IRS-2 deficiency in mice alters the expression and/or sensitivity of components of adrenergic signaling. PMID: 20959116
45. These data point to Irs2 as an important novel mediator of kidney size; deletion of Irs2 causes PKB/Akt phosphorylation-dependent decreases in GSK3beta activity. PMID: 20604929
46. By regulating the phosphorylation state of insulin receptors, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action PMID: 20028942
47. PKBalpha, but not PKBbeta or PKBgamma, is specifically activated by overexpression of IRS2 in beta-cells and is required for IRS2 action in the islets. PMID: 19933838
48. A predominant role of IRS-2 involved in insulin receptor signaling of 32D myeloid cells PMID: 19738441
49. results reveal a close relation between Pdx1 and Irs2, which suggests that dysregulation of Pdx1 might be a common element in autosomal early-onset (MODY) and common type 2 diabetes. PMID: 11994408
50. Overexpression of IRS2 in a T cell hybridoma does not protect the cells from activation-induced cell death. PMID: 12055235

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KEGG: mmu:384783

STRING: 10090.ENSMUSP00000038514

UniGene: Mm.407207