title: p87 and p101 subunits are distinct regulators determining class IB phosphoinositide 3-kinase (PI3K) specificity.
abstract: 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.
authors.affiliation: From the Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics and Interfaculty Centre of Pharmacogenomics and Pharmaceutical Research, University of Tübingen, 72074 Tübingen, Germany.
authors.forename: Aliaksei
authors.initials: A
authors.lastname: Shymanets
authors.lastname: Prajwal
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bucher
authors.forename: Sandra
authors.initials: S
authors.lastname: Beer-Hammer
authors.forename: Christian
authors.initials: C
authors.lastname: Harteneck
authors.forename: Bernd
authors.initials: B
authors.lastname: Nürnberg
mesh_terms: D000818:Animals; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D055503:Protein Multimerization / Q000502:physiology*; D061987:Sf9 Cells; D015398:Signal Transduction / Q000502:physiology*; D018411:Spodoptera; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D058544:Class Ib Phosphatidylinositol 3-Kinase
keywords: G-proteins; Gβγ p101; Phosphatidylinositol 3-Kinase; Phosphatidylinositol Signaling; Phosphoinositide 3-Kinase γ (PI3Kγ); Phospholipid; Signal Transduction; p87