Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations

Kouichi Inukai, Makoto Funaki, Motonobu Anai, Takehide Ogihara, Hideki Katagiri, Yasushi Fukushima, Hideyuki Sakoda, Yukiko Onishi, Hiraku Ono, Midori Fujishiro, Miho Abe, Yoshitomo Oka, Masatoshi Kikuchi, Tomoichiro Asano

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)32-38
Number of pages7
JournalFEBS Letters
Volume490
Issue number1-2
DOIs
Publication statusPublished - 2001 Feb 9

Keywords

  • Epidermal growth factor
  • Insulin
  • Phosphatidylinositol 3-kinase
  • Platelet-derived growth factor
  • Regulatory subunit

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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