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 (Comment) | Organism |
---|---|
p52shc and p66shc expression analysis, overexpression of p66shc | Homo sapiens |
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 | 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 | ? | - |
? | |
phosphorylated IGF-I receptor + H2O | Homo sapiens | isozyme p52shc | IGF-I receptor + phosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
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 | Comment | Organism | Textmining |
---|---|---|---|
smooth muscle cell | - |
Homo sapiens | - |
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 | ? | - |
? | |
phosphorylated IGF-I receptor + H2O | isozyme p52shc | Homo sapiens | IGF-I receptor + phosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
p52shc | - |
Homo sapiens |
p66shc | - |
Homo sapiens |
protein tyrosine phosphatase | - |
Homo sapiens |
protein tyrosine phosphatase-2 | - |
Homo sapiens |
SHP-2 | - |
Homo sapiens |
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 |