Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells

Nathalie Bonnefoy-Bérard, Yun Cai Liu, Maria Von Willebrand, Arthur Sung, Chris Elly, Tomas Mustelin, Hideaki Yoshida, Kimishige Ishizaka, Amnon Altman

Research output: Contribution to journalArticle

Abstract

Proteins of the 14-3-3 family can associate with, and/or modulate the activity of, several protooncogene and oncogene products and, thus, are implicated in regulation of signaling pathways. We report that 14-3-3 is associated with another important transducing enzyme, phosphatidylinositol 3- kinase (PI3-K). A recombinant 14-3-3 fusion protein bound several tyrosine- phosphorylated proteins from antigen receptor-stimulated T lymphocytes. PI3- K was identified by immunoblotting and enzymatic assays as one of the 14-3- 3-binding proteins in resting or activated cells. Moreover, endogenous 14-3- 3 and PI3-K were coimmunoprecipitated from intact T cells. Far-Western blots of gel-purified, immunoprecipitated PI3-K with a recombinant 14-3-3 fusion protein revealed direct binding of 14-3-3 to the catalytic subunit (p110) of PI3-K. Finally, anti-phosphotyrosine immunoprecipitates from activated, 14- 3-3-overexpressing cells contained lower PI3-K enzymatic activity than similar immunoprecipitates from control cells. These findings suggest that association of 14-3-3 with PI3-K in hematopoietic (and possibly other) cells regulates the enzymatic activity of PI3-K during receptor-initiated signal transduction.

Original languageEnglish (US)
Pages (from-to)10142-10146
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number22
DOIs
StatePublished - Oct 24 1995
Externally publishedYes

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Phosphatidylinositol 3-Kinase
14-3-3 Proteins
T-Lymphocytes
Recombinant Proteins
Far-Western Blotting
Phosphotyrosine
Antigen Receptors
Oncogene Proteins
Enzyme Assays
Immunoblotting
Tyrosine
Signal Transduction
Catalytic Domain
Carrier Proteins
Gels
Enzymes

Keywords

  • T-cell activation
  • tyrosine phosphorylation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells. / Bonnefoy-Bérard, Nathalie; Liu, Yun Cai; Von Willebrand, Maria; Sung, Arthur; Elly, Chris; Mustelin, Tomas; Yoshida, Hideaki; Ishizaka, Kimishige; Altman, Amnon.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 22, 24.10.1995, p. 10142-10146.

Research output: Contribution to journalArticle

Bonnefoy-Bérard, N, Liu, YC, Von Willebrand, M, Sung, A, Elly, C, Mustelin, T, Yoshida, H, Ishizaka, K & Altman, A 1995, 'Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 22, pp. 10142-10146. https://doi.org/10.1073/pnas.92.22.10142
Bonnefoy-Bérard, Nathalie ; Liu, Yun Cai ; Von Willebrand, Maria ; Sung, Arthur ; Elly, Chris ; Mustelin, Tomas ; Yoshida, Hideaki ; Ishizaka, Kimishige ; Altman, Amnon. / Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 22. pp. 10142-10146.
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