TY - JOUR
T1 - Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations
AU - Inukai, Kouichi
AU - Funaki, Makoto
AU - Anai, Motonobu
AU - Ogihara, Takehide
AU - Katagiri, Hideki
AU - Fukushima, Yasushi
AU - Sakoda, Hideyuki
AU - Onishi, Yukiko
AU - Ono, Hiraku
AU - Fujishiro, Midori
AU - Abe, Miho
AU - Oka, Yoshitomo
AU - Kikuchi, Masatoshi
AU - Asano, Tomoichiro
PY - 2001/2/9
Y1 - 2001/2/9
N2 - There are five isoforms of the regulatory subunit for the heterodimeric type of phosphatidylinositol 3-kinase. These five regulatory subunit isoforms were overexpressed using an adenovirus transfection system, and their own tyrosine phosphorylations and associations with various tyrosine kinase receptors were investigated. When overexpressed in CHO-PDGFR cells, the associations of these regulatory subunit isoforms with the platelet-derived growth factor receptor were similar. However, when overexpressed in CHO-IR cells, p55γ exhibited a significantly lower ability to bind with IRS-1 upon insulin stimulation, as compared with other regulatory subunit isoforms. Furthermore, p55α and p55γ were found to be tyrosine-phosphorylated. Finally, interestingly, when overexpressed in CHO-EGFR cells or A431 cells and stimulated with epidermal growth factor (EGF), phosphorylated EGF receptor was detected in p85α, p85β and p50α immunoprecipitates, but not in p55α and p55γ immunoprecipitates. In addition, EGF-induced tyrosine phosphorylation was observed in p85α, p85β, p55α and p55γ, but not in p50α, immunoprecipitates. Thus, each regulatory subunit exhibits specific responses regarding both the association with tyrosine-phosphorylated substrates and its own tyrosine phosphorylation. These results suggest that each isoform possesses specific roles in signal transduction, based on its individual tyrosine kinase receptor.
AB - There are five isoforms of the regulatory subunit for the heterodimeric type of phosphatidylinositol 3-kinase. These five regulatory subunit isoforms were overexpressed using an adenovirus transfection system, and their own tyrosine phosphorylations and associations with various tyrosine kinase receptors were investigated. When overexpressed in CHO-PDGFR cells, the associations of these regulatory subunit isoforms with the platelet-derived growth factor receptor were similar. However, when overexpressed in CHO-IR cells, p55γ exhibited a significantly lower ability to bind with IRS-1 upon insulin stimulation, as compared with other regulatory subunit isoforms. Furthermore, p55α and p55γ were found to be tyrosine-phosphorylated. Finally, interestingly, when overexpressed in CHO-EGFR cells or A431 cells and stimulated with epidermal growth factor (EGF), phosphorylated EGF receptor was detected in p85α, p85β and p50α immunoprecipitates, but not in p55α and p55γ immunoprecipitates. In addition, EGF-induced tyrosine phosphorylation was observed in p85α, p85β, p55α and p55γ, but not in p50α, immunoprecipitates. Thus, each regulatory subunit exhibits specific responses regarding both the association with tyrosine-phosphorylated substrates and its own tyrosine phosphorylation. These results suggest that each isoform possesses specific roles in signal transduction, based on its individual tyrosine kinase receptor.
KW - Epidermal growth factor
KW - Insulin
KW - Phosphatidylinositol 3-kinase
KW - Platelet-derived growth factor
KW - Regulatory subunit
UR - http://www.scopus.com/inward/record.url?scp=0035830778&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035830778&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(01)02132-9
DO - 10.1016/S0014-5793(01)02132-9
M3 - Article
C2 - 11172806
AN - SCOPUS:0035830778
VL - 490
SP - 32
EP - 38
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1-2
ER -