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PMID: 17470792 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 19 ·2007-05-08 ·Pages 7809-14

Geering B, Cutillas PR, Nock G, Gharbi SI, Vanhaesebroeck B

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 (p110alpha, p110beta, or p110delta) bound to any of five distinct regulatory subunits (p85alpha, p85beta, p55gamma, p55alpha, and p50alpha, 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) p85alpha 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 p110beta and p110delta 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.

MeSH Terms
Animals Catalytic Domain Dimerization Mass Spectrometry Mice Mice, Inbred C57BL NIH 3T3 Cells Phosphatidylinositol 3-Kinases/analysis,chemistry,genetics,physiology Protein Subunits RNA, Messenger/analysis Signal Transduction
Chemicals
Protein Subunits RNA, Messenger Phosphatidylinositol 3-Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Geering Barbara
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, United Kingdom.
Cutillas Pedro R
Nock Gemma
Gharbi Severine I
Vanhaesebroeck Bart
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0700373104
Published
2007-05-08
Epub
2007-00-30
Pages
7809-14
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1876529
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0700373104 PMC Full Text View journal details
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