p84 forms a negative regulatory complex with p110γ to control PI3Kγ signalling during cell migration

Immunology and Cell Biology
Michelle E TurveyShaun R McColl

Abstract

Phosphoinositide 3-kinase γ (PI3Kγ) consists of the catalytic subunit p110γ that forms a mutually exclusive heterodimer with one of the two adaptor subunits, p101 or p84. Although activation of PI3Kγ is necessary for cell migration downstream of G-protein-coupled receptor engagement, particularly within the immune system, aberrant PI3Kγ signalling has been associated with transformation, increased migration and the progression of multiple cancer types. Regulation of PI3Kγ signal activation and duration is critical to controlling and maintaining coordinated cellular migration; however, the mechanistic basis for this is not well understood. We have recently demonstrated that, in contrast to the tumour-promoting potential of p110γ and p101, p84 possesses tumour-suppressor activity, suggesting a negative regulatory role within PI3Kγ signalling. The present study investigated the role of p84 phosphorylation in the context of PI3Kγ signalling, cell migration and p84-mediated tumour suppression. Two putative phosphorylation sites were characterised within p84, Ser358 and Thr607. Expression of wild-type p84 reduced the oncogenic potential of MDA.MB.231 cells and inhibited metastatic lung colonisation in vivo, effects that were dependen...Continue Reading

References

May 5, 2001·The Journal of Biological Chemistry·B D CuevasG B Mills
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Michael HanniganChi-Kuang Huang
Jun 1, 2002·Science·Lewis C Cantley
Dec 22, 2004·The Journal of Biological Chemistry·Philipp VoigtMichael Schaefer
Sep 21, 2005·The Journal of Biological Chemistry·Chareeporn AkekawatchaiShaun R McColl
Jan 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sohye KangPeter K Vogt
Apr 17, 2009·Molecular & Cellular Proteomics : MCP·Felix S OppermannHenrik Daub
Oct 23, 2009·Nature·Anthony J TrimboliGustavo Leone
Nov 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Barbara KurigBernd Nürnberg
Dec 30, 2009·The Journal of Experimental Medicine·Michelle L JanasMartin Turner
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Heeseog KangDianqing Wu
Sep 21, 2010·Molecular Cancer·Sharon A WilliamsShaun R McColl
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jennifer Y LeeLewis C Cantley
Nov 8, 2011·The Biochemical Journal·Aliaksei ShymanetsBernd Nürnberg
Feb 24, 2012·Nature Reviews. Molecular Cell Biology·Bart VanhaesebroeckPhillip Hawkins
Mar 17, 2012·Nature Reviews. Genetics·Cédric Feschotte, Clément Gilbert
Apr 5, 2012·Nature Reviews. Molecular Cell Biology·Min Sup SongPier Paolo Pandolfi
Apr 21, 2012·Cancer Cell·Prem S SubramaniamThomas G Diacovo
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Jul 5, 2013·PLoS Biology·Romy WalserMatthias P Wymann
Sep 10, 2013·The Journal of Biological Chemistry·Aliaksei ShymanetsBernd Nürnberg
Sep 14, 2013·European Journal of Immunology·Nadia LadyginaWai-Ping Fung-Leung
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Oscar VadasRoger L Williams
Jul 17, 2014·Immunology and Cell Biology·Yuka Harata-LeeShaun R McColl

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Citations

May 30, 2019·Future Oncology·Anna M FrustaciMarco Montillo
Sep 5, 2019·Biomolecules·Bernd Nürnberg, Sandra Beer-Hammer
Jun 28, 2020·Journal of Tissue Engineering and Regenerative Medicine·Junsong JiangXuehong Liu

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