J Cell Physiol 1999,
PMID: 9886492
Takahashi, Y; Akanuma, Y; Yazaki, Y; Kadowaki, T
We recently described a better correlation of DNA synthesis with phosphatidylinositol (PI) 3-kinase than with mitogen-activated protein (MAP) kinase stimulated by insulin-like growth factor (IGF)-1 or epidermal growth factor (EGF) in human skin fibroblasts (Takahashi et al., 1997, Endocrinology 138:741-750). IGF-I-induced PI 3-kinase activation is generally mediated via insulin receptor substrate (IRS)-1, but EGF-induced PI 3-kinase activation is mediated by various signalling molecules such as ErbB3 and c-Cbl in different cells. We therefore investigated the mechanism regulating PI 3-kinase in human skin fibroblasts by comparing complexes involving PI 3-kinase when stimulated by IGF-I or EGF and found that p115 and p105, which were tyrosine-phosphorylated by EGF stimulation and associated with SHP-2, were also associated with the p85 subunit of PI 3-kinase by EGF. Anti-SHP-2 and anti-p85 subunits of PI 3-kinase antibodies did not coprecipitate tyrosine-phosphorylated EGF receptor or ErbB3; in addition, p115 and p105 appeared to be distinct from tyrosine-phosphorylated c-Cbl. Thus, tyrosine-phosphorylated p115 and p105 may provide a novel platform recruiting p85, which may simultaneously bind to SHP-2. In contrast, tyrosine phosphorylation of p115 or p 105 was undetectable by immunoblot with IGF-I stimulation, and PI 3-kinase activity was mediated via IRS-1 phosphorylated with IGF-I stimulation, little of which was associated with SHP-2. Thus, EGF and IGF-I cause formation of a distinct signalling complex which associates with p85 subunit of PI 3-kinase.
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Text Mining Data
PI 3-kinase → EGF: "
IGF-I induced PI 3-kinase activation is generally mediated via insulin receptor substrate (IRS)-1, but
EGF induced
PI 3-kinase activation is mediated by various signalling molecules such as ErbB3 and c-Cbl in different cells
"
PI 3-kinase → IGF-I: "
IGF-I induced PI 3-kinase activation is generally mediated via insulin receptor substrate (IRS)-1, but EGF induced PI 3-kinase activation is mediated by various signalling molecules such as ErbB3 and c-Cbl in different cells
"
PI 3-kinase → p 105: "
In contrast, tyrosine phosphorylation of p115 or p 105 was undetectable by immunoblot with IGF-I stimulation, and PI 3-kinase activity was mediated via IRS-1 phosphorylated with IGF-I stimulation, little of which was associated with SHP-2
"
PI 3-kinase → p115: "
In contrast, tyrosine phosphorylation of p115 or p 105 was undetectable by immunoblot with IGF-I stimulation, and PI 3-kinase activity was mediated via IRS-1 phosphorylated with IGF-I stimulation, little of which was associated with SHP-2
"
Manually curated Databases
-
IRef Biogrid Interaction:
PIK3R1
—
GRB2
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
GRB2
—
SHC1
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
PTPN11
—
PIK3R1
(physical association, affinity chromatography technology)
-
IRef Biogrid Interaction:
EGFR
—
GRB2
(physical association, affinity chromatography technology)
In total, 4 gene pairs are associated to this article in curated databases