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Literature summary for 3.1.3.48 extracted from

  • Xi, G.; Shen, X.; Clemmons, D.R.
    p66shc negatively regulates insulin-like growth factor I signal transduction via inhibition of p52shc binding to Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 leading to impaired growth factor receptor-bound protein-2 membrane (2008), Mol. Endocrinol., 22, 2162-2175.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
IGF-I IGF-I stimulates p52shc phosphorylation, with a significantly greater increase in p52shc phosphorylation in the p66shc knockdown cells compared to control cells. Overexpression of p66shc impairs IGF-I-stimulated p52shc tyrosine phosphorylation Homo sapiens
additional information formation of SHPS-1/SHP-2/Src/p52shc complex formation is essential for p52shc activity Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
p52shc and p66shc expression analysis, overexpression of p66shc Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information knockout of isozyme p66shc significantly enhances IGF-I-dependent SHPS-1/SHP-2/Src/p52shc/Grb2 complex formation, and p52shc tyrosine phosphorylation and Grb2 association, while overexpression inhibits it, overview. Disruption of the SHP-2/SHPS-1 complex is associated with a reduction in Src and SHPS-1 as well as Src and p52shc association Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens isozyme p52shc associates with the growth factor receptor-bound protein-2, Grb2. Overexpression of isozyme p66shc impaires IGF-I-stimulated p52shc tyrosine phosphorylation and p52shc-Grb2 association. Isozyme p66shc inhibits IGF-I signal transduction via competitively inhibiting the binding of Src homology 2 domain-containing SHP-2 to SHP substrate-1, leading to the disruption of SHPS-1/SHP-2/Src/p52shc complex formation, an event that is essential for p52shc phosphorylation and Grb2 recruitment, overview. p66shc inhibits IGF-I signal transduction via impairing membrane recruitment of Grb2 ?
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phosphorylated IGF-I receptor + H2O Homo sapiens isozyme p52shc IGF-I receptor + phosphate
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Organism

Organism UniProt Comment Textmining
Homo sapiens
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Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein p52 isoform of shc undergoes tyrosine phosphorylation after growth factor stimulation, which results in Grb2 recruitment and subsequent Ras and MAPK activation Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
smooth muscle cell
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Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information isozyme p52shc associates with the growth factor receptor-bound protein-2, Grb2. Overexpression of isozyme p66shc impaires IGF-I-stimulated p52shc tyrosine phosphorylation and p52shc-Grb2 association. Isozyme p66shc inhibits IGF-I signal transduction via competitively inhibiting the binding of Src homology 2 domain-containing SHP-2 to SHP substrate-1, leading to the disruption of SHPS-1/SHP-2/Src/p52shc complex formation, an event that is essential for p52shc phosphorylation and Grb2 recruitment, overview. p66shc inhibits IGF-I signal transduction via impairing membrane recruitment of Grb2 Homo sapiens ?
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?
phosphorylated IGF-I receptor + H2O isozyme p52shc Homo sapiens IGF-I receptor + phosphate
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?

Synonyms

Synonyms Comment Organism
p52shc
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Homo sapiens
p66shc
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Homo sapiens
protein tyrosine phosphatase
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Homo sapiens
protein tyrosine phosphatase-2
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Homo sapiens
SHP-2
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Homo sapiens

General Information

General Information Comment Organism
physiological function isozyme p52shc plays an essential role in mediating IGF-I activation of MAP kinases in smooth muscle cells, involving also protein tyrosine phosphatase-2, while isozyme p66shc inhibits IGF-I signal transduction, overview. p66shc functions to negatively regulate the formation of a signaling complex that is required for p52shc activation in response to IGF-I, thus leading to attenuation of IGF-I-stimulated cell proliferation and migration Homo sapiens