PIK3CG

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PIK3CG

A gene on chromosome 7q22.3 that encodes the gamma catalytic subunit of phosphoinositide-3-kinase (PI3K), which phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol-3,4,5-triphosphate (PIP3). This gamma catalytic subunit forms a heterodimer with PIK3R5 or PIK3R6 regulatory subunits; its interaction with ADRBK1 through the PIK helical domain is required for targeting to agonist-occupied receptor. It is thought to interact with PDE3B, TPM2 and EPHA8, and to regulate integrin-mediated cell adhesion to substrates.
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Fardella et al., "Lack of kinase-independent activity of PI3Kgamma in locus coeruleus induces ADHD symptoms through increased CREB signaling," EMBO Molecular Medicine, vol.
Sim et al., "PI3Kgamma is required for NMDA receptor-dependent long-term depression and behavioral flexibility," Nature Neuroscience, vol.
Naga Prasad, "Inhibition of protein phosphatase 2A activity by PI3Kgamma regulates beta-adrenergic receptor function," Molecular Cell, vol.
Diacovo, "Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils," European Journal of Immunology, vol.
Protection from angiotensin II-mediated vasculotoxic and hypertensive response in mice lacking PI3Kgamma. J Exp Med 2005; 201: 1217-1228, doi: 10.1084/jem.20040995.
Along with his colleagues, Professor Shaun McColl and PhD students Wendel Litchfield and Ervin Kara, he focused on a molecule known as PI3Kgamma, which is involved in the activation and movement of white blood cells.
"There's already been worldwide interest in PI3Kgamma in relation to other human inflammatory disorders, such as diabetes and rheumatoid arthritis, and our study links this molecule and MS," Dr Comerford said.
Following up on this result, the team then used an orally active drug that blocks the activity of the molecule PI3Kgamma at the first signs of disease onset.