Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85

P. Hu, A. Mondino, E. Y. Skolnik, J. Schlessinger

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Abstract

Phosphatidylinositol 3-kinase (PI 3-kinase) has been implicated as a participant in signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli. Here we describe the cloning of a novel and ubiquitously expressed human PI 3-kinase. The 4.8-kb cDNA encodes a putative translation product of 1,070 amino acids which is 42% identical to bovine PI 3-kinase and 28% identical to Vps34, a Saccharomyces cerevisiae PI 3-kinase involved in vacuolar protein sorting. Human PI 3-kinase is also similar to Tor2, a yeast protein required for cell cycle progression. Northern (RNA) analysis demonstrated expression of human PI 3-kinase in all tissues and cell lines tested. Protein synthesized from an epitope-tagged cDNA had intrinsic PI 3-kinase activity and associated with the adaptor 85-kDa subunit of PI 3-kinase (p85) in intact cells, as did endogenous human PI 3-kinase. Coprecipitation assays showed that a 187-amino-acid domain between the two src homology 2 domains of p85 mediates interaction with PI 3-kinase in vitro and in intact cells. These results demonstrate the existence of different PI 3-kinase isoforms and define a family of genes encoding distinct PI 3-kinase catalytic subunits that can associate with p85.

Original languageEnglish
Pages (from-to)7677-7688
Number of pages12
JournalMolecular and Cellular Biology
Volume13
Issue number12
Publication statusPublished - Dec 1993

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Phosphatidylinositol 3-Kinase
Organism Cloning
Binding Sites
Complementary DNA
Amino Acids
Fungal Proteins
src Homology Domains
Protein Transport
Saccharomyces cerevisiae
Epitopes

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85. / Hu, P.; Mondino, A.; Skolnik, E. Y.; Schlessinger, J.

In: Molecular and Cellular Biology, Vol. 13, No. 12, 12.1993, p. 7677-7688.

Research output: Contribution to journalArticle

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