ArticleThe Journal of biological chemistry2010
p66shc inhibits insulin-like growth factor-I signaling via direct binding to Src through its polyproline and Src homology 2 domains, resulting in impairment of Src kinase activation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress.Redox biology · 2024Article
- Heritable, Allele-Specific Chromosomal Looping between Tandem Promoters Specifies Promoter Usage ofMolecular and cellular biology · 2018Article
- Coupled regulation by the juxtamembrane and sterile α motif (SAM) linker is a hallmark of ephrin tyrosine kinase evolution.The Journal of biological chemistry · 2018Article
- p66Molecular and cellular biology · 2016Article
- Ouabain elicits human glioblastoma cells apoptosis by generating reactive oxygen species in ERK-p66SHC-dependent pathway.Molecular and cellular biochemistry · 2015Article
- A hypusine-eIF5A-PEAK1 switch regulates the pathogenesis of pancreatic cancer.Cancer research · 2014Article
- Aiolos promotes anchorage independence by silencing p66Shc transcription in cancer cells.Cancer cell · 2014Article
- Src tyrosine kinase signaling antagonizes nuclear localization of FOXO and inhibits its transcription factor activity.Scientific reports · 2014Article
- Arginase-II induces vascular smooth muscle cell senescence and apoptosis through p66Shc and p53 independently of its l-arginine ureahydrolase activity: implications for atherosclerotic plaque vulnerability.Journal of the American Heart Association · 2013Article
- Cellular functions regulated by phosphorylation of EGFR on Tyr845.International journal of molecular sciences · 2013Review
- Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membrane.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Mitochondrial longevity pathways.Biochimica et biophysica acta · 2011Review
- Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells.Cellular and molecular life sciences : CMLS · 2010Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
p66(shc) is increased in response to cell stress, and these increases regulate growth factor actions. These studies were conducted to determine how p66(shc) alters IGF-I-stimulated Src activation, leading to decreased IGF-I actions. Our results show that p66(shc) binds to Src through a polyproline sequence motif contained in the CH2 domain, a unique domain in p66(shc), and IGF-I stimulates this interaction. Disruption of this interaction using a synthetic peptide containing the p66(shc) polyproline domain or expression of a p66(shc) mutant containing substitutions for the proline residues (P47A/P48A/P50A) resulted in enhanced Src kinase activity, p52(shc) phosphorylation, MAPK activation, and cell proliferation in response to IGF-I. To determine the mechanism of inhibition, the full-length CH2 domain and intact p66(shc) were tested for their ability to directly inhibit Src kinase activation in vitro. The CH2 domain peptide was clearly inhibitory, but full-length p66(shc) had a greater effect. Deletion of the C-terminal Src homology 2 domain in p66(shc) reduced its ability to inhibit Src kinase activation. These findings demonstrate that p66(shc) utilizes a novel mechanism for modulating Src kinase activation and that this interaction is mediated through both its collagen homologous region 2 and Src homology 2 domains.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.