A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase structurally similar to p55PIK is generated by alternative splicing of the p85a gene

Kouichi Inukai, Motonobu Anai, Eric Van Breda, Toshio Hosaka, Hideki Katagiri, Makoto Funaki, Yasushi Fukushima, Takehide Ogihara, Yoshio Yazaki, Masatoshi Kikuchi, Yoshitomo Oka, Tomoichiro Asano

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Phosphatidylinositol 3-kinase, which is composed of a 110-kDa catalytic subunit and a regulatory subunit, plays important roles in various cellular signaling mechanisms. We screened a rat brain cDNA expression library with 32P-labeled human IRS-1 protein and cloned cDNAs that were very likely to be generated by alternative splicing of p85α gene products. These cDNAs were demonstrated to encode a 55-kDa protein (p55α) containing two SH2 domains and an inter-SH2 domain of p85a but neither a bcr domain nor a SH3 homology domain. Interestingly, p55a contains a unique 34-amino acid sequence at its NH2 terminus, which is not included in the p85a amino acid sequence. This 34-amino acid portion was revealed to be comparable with p55PIK (p55γ) in length, with a high homology between the two, suggesting that these NH2-terminal domains of p55α and p55γ may have a specific role that p85 does not. The expression of p55a mRNA is most abundant in the brain, but expression is ubiquitous in most rat tissues. Furthermore, it should be noted that the expression of p85α mRNA in muscle is almost undetectably low by Northern blotting with a cDNA probe coding for the p85α SH3 domain, while the expression of p55α can be readily detected. These results suggest that p55α may play an unique regulatory role for phosphatidylinositol 3-kinase in brain and muscle.

Original languageEnglish
Pages (from-to)5317-5320
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number10
DOIs
Publication statusPublished - 1996 Mar 8
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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