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Cited by 225

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Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers

Open access
Geering, Barbara, Cutillas, Pedro R., Nock, Gemma, Gharbi, Severine I., Vanhaesebroeck, Bart·2007·Proceedings of the National Academy of Sciences

Abstract

Class IA phosphoinositide 3-kinases (PI3Ks) signal downstream of tyrosine kinases and Ras and control a wide variety of biological responses. In mammals, these heterodimeric PI3Ks consist of a p110 catalytic subunit (p110α, p110β, or p110δ) bound to any of five distinct regulatory subunits (p85α, p85β, p55γ, p55α, and p50α, collectively referred to as “p85s”). The relative expression levels of p85 and p110 have been invoked to explain key features of PI3K signaling. For example, free (i.e., non-p110-bound) p85α has been proposed to negatively regulate PI3K signaling by competition with p85/p110 for recruitment to phosphotyrosine docking sites. Using affinity and ion exchange chromatography and quantitative mass spectrometry, we demonstrate that the p85 and p110 subunits are present in equimolar amounts in mammalian cell lines and tissues. No evidence for free p85 or p110 subunits could be obtained. Cell lines contain 10,000–15,000 p85/p110 complexes per cell, with p110β and p110δ being the most prevalent catalytic subunits in nonleukocytes and leukocytes, respectively. These results argue against a role of free p85 in PI3K signaling and provide insights into the nonredundant functions of the different class IA PI3K isoforms.

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Metadata

Authors
Geering, B., Cutillas, P. R., Nock, G., Gharbi, S. I., & Vanhaesebroeck, B.
Venue
Proceedings of the National Academy of Sciences
Published
2007-05-08
Volume
104
Issue
19
Pages
7809-7814
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2046571983
Cited by
225
References
6
FWCI
5.63
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. https://app.cochat.ai/papers/10.1073/pnas.0700373104
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Geering, B., Cutillas, P. R., Nock, G., Gharbi, S. I., & Vanhaesebroeck, B. (2007). Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0700373104

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