Recombinant Mouse SHC-transforming protein 1 (Shc1)

1. Study in MMTV/MT6 and MMTV/NIC breast cancer mouse models show that ShcA phosphotyrosine motifs potentiate immune suppression by limiting signal transducer and activator of transcription (STAT)-1-driven anti-tumour immunity, while simultaneously increasing STAT3 immunosuppressive signals. PMID: 28276425
2. Sirt3 modulates age-associated mitochondrial biology and function via lysine deacetylation of target proteins, and authors show that its regulation depends on its nitration status and is benefited by the improved NAD(+)/NADH ratio in aged p66(Shc(-/-)) brain mitochondria. PMID: 29721150
3. miR-200c might be responsible for muscle wasting and myotube loss, most probably via a p66Shc-dependent mechanism in a pathological disease such as Duchenne muscular dystrophy. PMID: 29636844
4. Data show that 66-kDa Src homology 2 domain-containing protein (p66Shc) is acetylated under high glucose conditions and is deacetylated by Sirtuin1 lysine deacetylase (Sirt1) on lysine 81. PMID: 28137876
5. a pivotal role for p66(shc) -induced vascular dysfunction in a common pathogenic cascade shared by noise-induced and age-related hearing loss, is reported. PMID: 27157635
6. P66Shc, a key regulator of metabolism and mitochondrial ROS production, is dysregulated by mouse embryo culture PMID: 27385725
7. The results indicate that Shc proteins should be considered as potential targets for developing interventions to mitigate weight gain on high-fat diet by stimulating energy expenditure. PMID: 29243276
8. Hyperglycemia and elevated free fatty acids in the diabetic milieu recruit p66Shc to upregulate endothelial miR-34a via an oxidant-sensitive mechanism, which leads to endothelial dysfunction by targeting Sirt1. PMID: 27789474
9. p66SHC-mediated oxidative stress and telomere shortening synergize in some tissues (including testes) to accelerate aging. PMID: 26968134
10. Taken together, these data argue for a complex mechanism of PKCbeta-dependent regulation of p66 activation involving Ser(139) and a motif surrounding Ser(213). PMID: 27624939
11. JNK1/2-dependent regulation of p66ShcS36 phosphorylation, is reported. PMID: 26868434
12. Data show that the major mitochondrial partner of Shc adaptor protein p46Shc is the lipid oxidation enzyme 3-ketoacylCoA thiolase ACAA2, to which p46Shc binds directly and with a strong affinity. PMID: 27059956
13. In mice and humans, reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin resistance. PMID: 26122877
14. p53-dependent augmentation of p66(Shc) expression and function represents a key signalling response contributing to beta cell apoptosis under conditions of lipotoxicity PMID: 25810038
15. Results show that genetic deletion of p66(Shc) increased susceptibility to myocardial injury in response to short-term ischaemia and reperfusion in mice PMID: 25336219
16. myocardial infarction transiently induced expression and phosphorylation of cardiac p66ShcA in mice PMID: 25680868
17. Silencing of p66(Shc) restored insulin response via IRS-1/Akt/eNOS pathway. Its knockdown in endothelial cells from Ob/Ob mice lessened ROS production, FFA oxidation, and dysregulation of redox-sensitive pathways. PMID: 25150941
18. These data identify multiple modes by which ShcA can fine-tune the development of early thymocytes, including a previously unappreciated ShcA-c-Abl axis that regulates thymocyte proliferation. PMID: 25691660
19. PKCbeta2 inhibition protects mice from gut ischemia-reperfusion injury by suppressing the adaptor p66(Shc)-mediated oxidative stress and subsequent apoptosis. PMID: 24722289
20. Endothelial function in cerebral arteries is heavily impaired by aging and is partly mediated by the p66Shc gene. PMID: 25012499
21. ShcA interacts with crucial proteins and pathways that link Z-disk and costamere during heart development PMID: 25488665
22. these data identify an important role for the adapter protein ShcA in later stages of thymic T cell development and in peripheral T cell-dependent events. PMID: 25595778
23. CRIF1 knockdown partially induces endothelial activation via increased ROS production and phosphorylation of p66shc PMID: 24906005
24. The regulation of p66shc-related antioxidative and antiapoptotic factors contributes to protection from ischemia-reperfusion injury. PMID: 24757420
25. p66Shc is not a longevity protein. However, additional studies are needed to determine the extent to which Shc proteins may influence the onset and severity of specific age-related diseases. PMID: 24336818
26. p66(Shc) plays a vital part in canonical Wnt signaling in the endothelium and mediates Wnt3a-stimulated endothelial oxidative stress and dysfunction. PMID: 25147340
27. study identifies p66ShcA as one of the first prognostic biomarkers for the identification of more aggressive tumors with mesenchymal properties, regardless of molecular subtype. PMID: 25071152
28. Higher sensitivity of the male kidney to AKI may be due to the testosterone-dependent increase in p66shc expression. PMID: 24632974
29. This study thus identifies a previously unrecognized role for p66Shc in the regulation of PTP oxidation controlling growth factor-induced signaling and migration. PMID: 24378437
30. Results identify p66Shc as a negative regulator of B-cell chemotaxis and suggest a role for this adaptor in the control of B-cell homing via CXCR4/5. PMID: 24556683
31. unlike the other isoforms of Shc1, p66Shc appears to antagonize insulin and mTOR signaling, which limits glucose uptake and metabolism. PMID: 24550542
32. study concludes hypercholesterolemia stimulates p66Shc expression in platelets, promoting platelet oxidative stress, hyperreactivity and hyperaggregation via p66Shc PMID: 24845561
33. Deletion of p66Shc protects from experimental autoimmune encephalomyelitis without affecting immune response. PMID: 23766859
34. autonomic neuropathy in the bone marrow impairs stem cell mobilization in diabetes with dysregulation of the life-span regulators p66Shc and Sirt1 PMID: 24270983
35. p66shc has a role in renal toxicity of oleic acid PMID: 23988748
36. Arg-II promotes mitochondrial dysfunction leading to VSMC senescence/apoptosis through complex positive crosstalk among S6K1-JNK, ERK, p66Shc, and p53, contributing to atherosclerotic vulnerability phenotype. PMID: 23832324
37. Lung p66(Shc) attenuates epithelial proliferation while promoting both distal and proximal epithelial maturation. PMID: 24375794
38. These findings identify p66Shc as a critical regulator of actin dynamics in mast cells. PMID: 24078705
39. P66Shc represents a clear example of an antagonistic pleiotropic function, which generates both beneficial (thermoregulation control) and detrimental ROS generation) phenomena in an organism. PMID: 23849861
40. Increased phosphorylation of p66shc is associated with renal oxidative stress and injury. PMID: 23328708
41. Salvianolic acid A induced SIRT1 plays an anti-apoptotic role in concanavalin A induced hepatitis by inhibiting p66Shc expression. PMID: 23993977
42. mice, p66Shc contributes to tumor initiation, in particular upon activation by carcinogens as well as when p53- mediated tumor suppression mechanisms defect PMID: 23092318
43. oxidative stress activates a specific p53 transcriptional response, mediated by p44/p53 and p66, which regulates cellular senescence and aging. PMID: 23448364
44. Shc1 scaffold therefore directs the temporal flow of signalling information after EGF stimulation PMID: 23846654
45. Distinct phosphotyrosine-dependent functions of the ShcA adaptor protein are required for transforming growth factor beta (TGFbeta)-induced breast cancer cell migration, invasion, and metastasis PMID: 23277357
46. Null mutations at the p66 and bradykinin 2 receptor loci induce divergent phenotypes in the diabetic kidney in mice. PMID: 23019230
47. Protocatechuic acid treatment down-regulated p66shc expression and reduced I/R-induced lung injury in mice, reinforcing the role p66shc plays in apoptosis. PMID: 23117377
48. Data show that hydrogen peroxide (H2O2) activates a protein kinase C beta/p66(shc)/NF-kappaB cascade and that p66(shc) is an essential mediator of the stimulating effects of H2O2 on apoptosis of osteoblastic cells as well as their ability to activate NF-kappaB. PMID: 20685851
49. The results indicated that p66Shc does not significantly influence energy expenditure in 18mo mice at baseline or 2 mo of caloric restriction, although it may play a role in the energy expenditure response to very acute caloric restriction. PMID: 22588161
50. Mitochondrial adaptor p66(Shc) is the key effector driving vascular hyperglycemic memory in experimental diabetes mellitus. PMID: 22693349

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KEGG: mmu:20416

STRING: 10090.ENSMUSP00000091940

UniGene: Mm.86595