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Isoform b of DDR1 (show DDR1 Proteins) is responsible for collagen I-induced up-regulation of N-cadherin (show CDH2 Proteins) and tyrosine 513 of DDR1b is necessary.
NIC (show NCSTN Proteins) exacerbated AZA-dependent injury via augmenting p66shc transcription. While RES suppressed NIC (show NCSTN Proteins)+AZA-mediated injury, -surprisingly-it further enhanced activity of the p66shc promoter. RES protected cells via the cytoplasmic p66shc/Nrf2 (show GABPA Proteins)/heme oxygenase-1 (HO-1 (show HMOX1 Proteins)) axis
The results show that the interaction between STS-1 (show STS1 Proteins) and ShcA is regulated in response to EGF receptor (show EGFR Proteins) activation.
Nox4 (show NOX4 Proteins)-derived H2O2 in part activates Nox2 (show CYBB Proteins) to increase mitochondrial ROS (show ROS1 Proteins) via pSer36-p66Shc, thereby enhancing VEGFR2 (show KDR Proteins) signaling and angiogenesis in endothelial cells.
Taken together, these data argue for a complex mechanism of PKC-beta-dependent regulation of SH (show POLD3 Proteins)CA (p66) activation invol (show SIGLEC1 Proteins)ving Ser(139) and a motif surroun (show SIGLEC1 Proteins)ding Ser(213).
Data identify, for the first time, a novel non-canonical dynamic mode of interaction between Met and the p66 (show POLD3 Proteins) protein isoform of Shc and its effects on rewiring binding effector complexes according to the activation state of the receptor.
regulates the alternative splicing of XAF1 (show XAF1 Proteins) in extracellular matrix-detachment induced autophagy to coordinate with the anoikic cell death
The silence of p66(Shc) in HCT8 cells reduced the proliferation and accelerated the apoptosis, in addition, the expression of pro-apoptotic proteins caspase-3 (show CASP3 Proteins), caspase-9 (show CASP9 Proteins), Bax (show BAX Proteins) was enhanced and the expression of anti-apoptotic protein Bcl-2 (show BCL2 Proteins) was declined.
In mice and humans, reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin (show INS Proteins) resistance.
Data suggest SHC1 (SH2 domain protein C1) expression down-regulates epithelial-mesenchymal transition by repressing TGFB (show TGFB1 Proteins)-induced SMAD2 (show SMAD2 Proteins)/3 activation through differential partitioning of receptors at cell surface of mammocytes/keratinocytes.
Data show that adaptor protein Shc is required for angiogenesis in zebrafish (accession number LOC563639), mice, and human vascular endothelial cell-culture models.
ShcA is required for Wnt-5a (show WNT5A Proteins)/Ror2 (show ROR2 Proteins) mediated upregulation of xPAPC (show PCDH8 Proteins), which demonstrates the functional relevance of this interaction.
Studied p66Shc levels, redox state, and developmental potential in early bovine embryos. p66Shc content was increased by either high (20%) O(2) culture or H(2)O(2) treatment, and significantly dec'd by antioxidant polyethylene glycol-conjugated catalase (show CAT Proteins).
p66shc, but not p53 (show TP53 Proteins), is significantly more abundant in an embryo population that exhibits higher frequencies of embryo arrest.
p66Shc is involved in the regulation of embryo development specifically in mediating early cleavage arrest and facilitating development to the blastocyst stage for in vitro produced bovine embryos
These results support a model in which Shc orchestrates signals from cell-cell and cell-matrix adhesions to elicit flow-induced inflammatory signaling.
Hyperglycemia and elevated free fatty acids in the diabetic milieu recruit p66Shc to upregulate endothelial miR (show MLXIP Proteins)-34a via an oxidant-sensitive mechanism, which leads to endothelial dysfunction by targeting Sirt1 (show SIRT1 Proteins).
p66SHC-mediated oxidative stress and telomere shortening synergize in some tissues (including testes) to accelerate aging.
Taken together, these data argue for a complex mechanism of PKCbeta-dependent regulation of p66 (show POLD3 Proteins) activation involving Ser (show SIGLEC1 Proteins)(139) and a motif surrounding Ser (show SIGLEC1 Proteins)(213).
JNK1 (show MAPK8 Proteins)/2-dependent regulation of p66ShcS36 phosphorylation, is reported.
Data show that the major mitochondrial partner of Shc adaptor protein p46Shc is the lipid oxidation enzyme 3-ketoacylCoA thiolase (show HADHB Proteins) ACAA2 (show ACAA2 Proteins), to which p46Shc binds directly and with a strong affinity.
p53 (show TP53 Proteins)-dependent augmentation of p66(Shc) expression and function represents a key signalling response contributing to beta cell apoptosis under conditions of lipotoxicity
Silencing of p66(Shc) restored insulin (show INS Proteins) response via IRS-1 (show IRS1 Proteins)/Akt (show AKT1 Proteins)/eNOS (show NOS3 Proteins) pathway. Its knockdown in endothelial cells from Ob/Ob mice lessened ROS (show ROS1 Proteins) production, FFA oxidation, and dysregulation of redox-sensitive pathways.
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.
PKCbeta2 inhibition protects mice from gut (show GUSB Proteins) ischemia-reperfusion injury by suppressing the adaptor p66(Shc)-mediated oxidative stress and subsequent apoptosis.
This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene.
SHC (Src homology 2 domain containing) transforming protein 1
, Sporulation-specific activator of Chs3p (chitin synthase III), required for the synthesis of the chitosan layer of ascospores; has similarity to Skt5p, which activates Chs3p during vegetative growth; transcriptionally induced at alkaline pH
, squalene--hopene cyclase
, SH2 domain protein C1
, SHC-transforming protein 1
, src homology 2 domain-containing-transforming protein C1
, SHC-transforming protein 1-like
, SHC (Src homology 2 domain-containing) transforming protein 1
, SHC-transforming protein 3
, SHC-transforming protein A
, src homology 2 domain-containing transforming protein C1
, src homology collagen
, adaptor protein SHC