p85/p110-type phosphatidylinositol kinase phosphorylates not only the D- 3, but also the D-4 position of the inositol ring

Makoto Funaki, Hideki Katagiri, Akira Kanda, Motonobu Anai, Masao Nawano, Takehide Ogihara, Kouichi Inukai, Yasushi Fukushima, Hiraku Ono, Yoshio Yazaki, Masatoshi Kikuchi, Yoshitomo Oka, Tomoichiro Asano

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Activation of p85/p110-type phosphatidylinositol (PI) kinase has been implicated in various cellular activities. This PI kinase phosphorylates the D-4 position with a similar or higher efficiency than the D-3 position when trichloroacetic acid-treated cell membrane is used as a substrate, although it phosphorylates almost exclusively the D-3 position of the inositol ring in phosphoinositides when purified PI is used as a substrate. Furthermore, the lipid kinase activities of p110 for both the D-3 and D-4 positions were completely abolished by introducing kinase-dead point mutations in their lipid kinase domains (ΔKinα and δKinβ, respectively). In addition, both PI 3- and PI 4-kinase activities of pl10α and pl101β immunoprecipitates were similarly inhibited by either wortmannin or LY294002, specific inhibitors of pl10. Insulin induced phosphorylation of not only the D-3 position, but also the D-4 position. Indeed, overexpression of pl10 in Sf9 or 3T3-L1 cells induced marked phosphorylation of the D-4 position to a level comparable to or much greater than that of D-3, whereas inhibition of endogenous p85/pl10-type PI kinase via overexpression of dominant-negative p85α (Δp85α) in 3T3-L1 adipocytes abolished insulin-induced synthesis of both. Thus, p85/pl10-type PI kinase phosphorylates the D-4 position of phosphoinositides more efficiently than the D-3 position in vivo, and each of the D-3- or D-4-phosphorylated phosphoinositides may transmit signals downstream.

Original languageEnglish
Pages (from-to)22019-22024
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number31
DOIs
Publication statusPublished - 1999 Jul 30

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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