p87 and p101 Subunits Are Distinct Regulators Determining Class IB Phosphoinositide 3-Kinase (PI3K) Specificity
| Autor: | Sandra Beer-Hammer, Aliaksei Shymanets, Prajwal, Bernd Nürnberg, Christian Harteneck, Kirsten Bucher |
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| Rok vydání: | 2013 |
| Předmět: |
Male
G protein Protein subunit Class Ib Phosphatidylinositol 3-Kinase Spodoptera Biochemistry Gene Expression Regulation Enzymologic Substrate Specificity Sf9 Cells Animals Humans Molecular Biology PI3K/AKT/mTOR pathway Phosphoinositide 3-kinase biology HEK 293 cells Cell Biology In vitro Cell biology HEK293 Cells biology.protein Female Protein Multimerization Signal transduction Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 288:31059-31068 |
| ISSN: | 0021-9258 |
| Popis: | Class IB phosphoinositide 3-kinase γ (PI3Kγ) comprises a single catalytic p110γ subunit, which binds to two non-catalytic subunits, p87 or p101, and controls a plethora of fundamental cellular responses. The non-catalytic subunits are assumed to be redundant adaptors for Gβγ enabling G-protein-coupled receptor-mediated regulation of PI3Kγ. Growing experimental data provide contradictory evidence. To elucidate the roles of the non-catalytic subunits in determining the specificity of PI3Kγ, we tested the impact of p87 and p101 in heterodimeric p87-p110γ and p101-p110γ complexes on the modulation of PI3Kγ activity in vitro and in living cells. RT-PCR, biochemical, and imaging data provide four lines of evidence: (i) specific expression patterns of p87 and p101, (ii) up-regulation of p101, providing the basis to consider p87 as a protein forming a constitutively and p101 as a protein forming an inducibly expressed PI3Kγ, (iii) differences in basal and stimulated enzymatic activities, and (iv) differences in complex stability, all indicating apparent diversity within class IB PI3Kγ. In conclusion, expression and activities of PI3Kγ are modified differently by p87 and p101 in vitro and in living cells, arguing for specific regulatory roles of the non-catalytic subunits in the differentiation of PI3Kγ signaling pathways. Background: p87 and p101 represent non-catalytic subunits of class IB PI3Kγ. Results: Expression and activity of PI3Kγ is modified differently by p87 and p101 in vitro and in living cells. Conclusion: Non-catalytic subunits of PI3Kγ represent two different regulators in the absence of Gβγ or Ras. Significance: p87 and p101 determine diversity within class IB PI3Kγ and allow integration in distinct PI3Kγ signaling pathways. |
| Databáze: | OpenAIRE |
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