Signaling by the Phosphoinositide 3-Kinase Family in Immune Cells
TLDR
The understanding of the PI3Ks in immunity is guided by fundamental discoveries made in simpler model organisms as well as by appreciating new adaptations of this signaling module in mammals in general and in immune cells in particular.Abstract:
Phosphoinositide 3-kinases (PI3Ks) control many important aspects of immune cell development, differentiation, and function. Mammals have eight PI3K catalytic subunits that are divided into three classes based on similarities in structure and function. Specific roles for the class I PI3Ks have been broadly investigated and are relatively well understood, as is the function of their corresponding phosphatases. More recently, specific roles for the class II and class III PI3Ks have emerged. Through vertebrate evolution and in parallel with the evolution of adaptive immunity, there has been a dramatic increase not only in the genes for PI3K subunits but also in genes for phosphatases that act on 3-phosphoinositides and in 3-phosphoinositide-binding proteins. Our understanding of the PI3Ks in immunity is guided by fundamental discoveries made in simpler model organisms as well as by appreciating new adaptations of this signaling module in mammals in general and in immune cells in particular.read more
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Journal ArticleDOI
The PI3K pathway in human disease
David A. Fruman,Honyin Chiu,Benjamin D. Hopkins,Shubha Bagrodia,Lewis C. Cantley,Robert T. Abraham +5 more
TL;DR: A perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions is provided, two topics closely intertwined with cancer biology.
Journal ArticleDOI
PI3K and cancer: lessons, challenges and opportunities
David A. Fruman,Christian Rommel +1 more
TL;DR: Through a greater focus on patient selection, increased understanding of immune modulation and strategic application of rational combinations, it should be possible to realize the potential of this promising class of targeted anticancer agents.
Journal ArticleDOI
Targeting PI3K in cancer: mechanisms and advances in clinical trials
TL;DR: A critical review is performed to summarize the role of the PI3K pathway in tumor development, recentPI3K inhibitors development based on clinical trials, and the mechanisms of resistance to PI3k inhibition.
Journal ArticleDOI
Phosphoinositide 3-Kinase δ Gene Mutation Predisposes to Respiratory Infection and Airway Damage
Ivan Angulo,Oscar Vadas,Fabien Garçon,Edward Banham-Hall,Vincent Plagnol,Timothy Ronan Leahy,Timothy Ronan Leahy,Helen Baxendale,Tanya I. Coulter,Tanya I. Coulter,James Curtis,Changxin Wu,Katherine G. Blake-Palmer,Olga Perisic,Deborah J. Smyth,Mailis Maes,Christine A Fiddler,Jatinder K. Juss,Deirdre Cilliers,Gašper Markelj,Anita Chandra,George Farmer,Anna Kielkowska,Jonathan Clark,Sven Kracker,Sven Kracker,Marianne Debré,Capucine Picard,Capucine Picard,Isabelle Pellier,Nada Jabado,James Morris,Gabriela Barcenas-Morales,Alain Fischer,Alain Fischer,Len R. Stephens,Phillip T. Hawkins,Jeffrey C. Barrett,Mario Abinun,Menna R. Clatworthy,Anne Durandy,Rainer Doffinger,Edwin R. Chilvers,Andrew J. Cant,Dinakantha S. Kumararatne,Klaus Okkenhaug,Roger L. Williams,Alison M. Condliffe,Sergey Nejentsev +48 more
TL;DR: Activated PI3K-δ syndrome (APDS), a PID associated with a dominant gain-of-function mutation in which lysine replaced glutamic acid at residue 1021 (E1021K) in the p110δ protein, the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), encoded by the PIK3CD gene is described.
Journal ArticleDOI
Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer
Khaled Ali,Dalya R. Soond,Roberto Piñeiro,Thorsten Hagemann,Wayne Pearce,Ee Lyn Lim,Hicham Bouabe,Cheryl L. Scudamore,Timothy Hancox,Heather Maecker,Lori Friedman,Martin R Turner,Klaus Okkenhaug,Bart Vanhaesebroeck +13 more
TL;DR: It is reported that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours, and can break tumour-induced immune tolerance and should be considered for wider use in oncology.
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Platanias,Stefanie Pöggeler,Marc Poirot,Angelo Poletti,Christian Poüs,Mercedes Pozuelo-Rubio,Mette Prætorius-Ibba,Anil Prasad,Mark Prescott,Muriel Priault,Nathalie Produit-Zengaffinen,Ann Progulske-Fox,Tassula Proikas-Cezanne,Serge Przedborski,Karin Przyklenk,Rosa Puertollano,Julien Puyal,Shu-Bing Qian,Liang Qin,Zheng-Hong Qin,Susan E. Quaggin,Nina Raben,Hannah Rabinowich,Simon W. Rabkin,Irfan Rahman,Abdelhaq Rami,Georg Ramm,Glenn Randall,Felix Randow,V. Ashutosh Rao,Jeffrey C. Rathmell,Brinda Ravikumar,Swapan K. Ray,Bruce H. Reed,John C. Reed,Fulvio Reggiori,Anne Régnier-Vigouroux,Anne Régnier-Vigouroux,Andreas S. Reichert,John J. Reiners,Russel J. Reiter,Jun Ren,José L. Revuelta,Christopher J. Rhodes,Konstantinos Ritis,Elizete Rizzo,Jeffrey Robbins,Michel Roberge,Hernan Roca,Maria Carmela Roccheri,Stéphane Rocchi,H. Peter Rodemann,Santiago Rodríguez de Córdoba,Bärbel Rohrer,Igor B. Roninson,Kirill V. Rosen,Magdalena Rost-Roszkowska,Mustapha Rouis,Kasper M.A. Rouschop,Francesca Rovetta,Brian P. Rubin,David C. Rubinsztein,Klaus Ruckdeschel,Edmund B. Rucker,Assaf Rudich,Emil Rudolf,Nelson Ruiz-Opazo,Rossella Russo,Tor Erik Rusten,Kevin M. Ryan,Stefan W. Ryter,David M. Sabatini,Junichi Sadoshima,Tapas Saha,Tatsuya Saitoh,Hiroshi Sakagami,Yasuyoshi Sakai,Ghasem Hosseini Salekdeh,Paolo Salomoni,Paul M. Salvaterra,Guy S. Salvesen,Rosa Salvioli,Anthony Sanchez,José Antonio Sánchez-Alcázar,Ricardo Sánchez-Prieto,Marco Sandri,Uma Sankar,Poonam Sansanwal,Laura Santambrogio,Shweta Saran,Sovan Sarkar,Minnie M. Sarwal,Chihiro Sasakawa,Ausra Sasnauskiene,Miklós Sass,Ken Sato,Miyuki Sato,Anthony H.V. Schapira,Michael Scharl,Hermann M. Schätzl,Wiep Scheper,Stefano Schiaffino,Claudio Schneider,Marion Schneider,Regine Schneider-Stock,Patricia V. Schoenlein,Daniel F. Schorderet,Christoph Schüller,Gary K. Schwartz,Luca Scorrano,Linda Sealy,Per Ottar Seglen,Juan Segura-Aguilar,Iban Seiliez,Oleksandr Seleverstov,Christian Sell,Jong Bok Seo,Duska Separovic,Vijayasaradhi Setaluri,Takao Setoguchi,Carmine Settembre,John J. Shacka,Mala Shanmugam,Irving M. Shapiro,Eitan Shaulian,Reuben J. Shaw,James H. Shelhamer,Han-Ming Shen,Wei-Chiang Shen,Zu-Hang Sheng,Yang Shi,Kenichi Shibuya,Yoshihiro Shidoji,Jeng-Jer Shieh,Chwen Ming Shih,Yohta Shimada,Shigeomi Shimizu,Takahiro Shintani,Orian S. Shirihai,Gordon C. Shore,Andriy A. Sibirny,Andriy A. Sibirny,Stan B. Sidhu,Beata Sikorska,Elaine C.M. Silva-Zacarin,Alison Simmons,Anna Katharina Simon,Hans-Uwe Simon,Cristiano Simone,Anne Simonsen,David A. Sinclair,Rajat Singh,Debasish Sinha,Frank A. Sinicrope,Agnieszka Sirko,Parco M. Siu,Efthimios Sivridis,Vojtech Skop,Vladimir P. Skulachev,Ruth S. Slack,Soraya S. Smaili,Duncan R. Smith,Maria S. Soengas,Thierry Soldati,Xueqin Song,Anil K. Sood,Tuck Wah Soong,Federica Sotgia,Stephen A. Spector,Stephen A. Spector,Claudia Spies,Wolfdieter Springer,Srinivasa M. Srinivasula,Leonidas Stefanis,Joan S. Steffan,Ruediger Stendel,Harald Stenmark,Anastasis Stephanou,Stephan T. Stern,Cinthya Sternberg,Björn Stork,Peter Strålfors,Carlos S. Subauste,Xinbing Sui,David Sulzer,Jiaren Sun,Shi-Yong Sun,Zhi Jun Sun,Joseph J.Y. Sung,Kuninori Suzuki,Toshihiko Suzuki,Michele S. Swanson,Charles Swanton,Sean T. Sweeney,Lai King Sy,Gyorgy Szabadkai,Ira Tabas,Heinrich Taegtmeyer,Marco Tafani,Krisztina Takács-Vellai,Yoshitaka Takano,Kaoru Takegawa,Genzou Takemura,Fumihiko Takeshita,Nicholas J. Talbot,Kevin S. W. Tan,Keiji Tanaka,Kozo Tanaka,Daolin Tang,Dingzhong Tang,Isei Tanida,Bakhos A. Tannous,Nektarios Tavernarakis,Graham S. Taylor,Gregory A. Taylor,J. Paul Taylor,Ance S. Terada,Alexei Terman,Gianluca Tettamanti,Karin Thevissen,Craig B. Thompson,Andrew Thorburn,Michael Thumm,Feng Feng Tian,Yuan Tian,Glauco P. Tocchini-Valentini,Aviva M. Tolkovsky,Yasuhiko Tomino,Lars Tönges,Sharon A. Tooze,Cathy Tournier,John Tower,Roberto Towns,Vladimir Trajkovic,Leonardo H. Travassos,Ting Fen Tsai,Mario P. Tschan,Takeshi Tsubata,Allan Tsung,Boris Turk,Lorianne S. Turner,Suresh C. Tyagi,Yasuo Uchiyama,Takashi Ueno,Midori Umekawa,Rika Umemiya-Shirafuji,Vivek K. Unni,Maria I. Vaccaro,Enza Maria Valente,Enza Maria Valente,Greet Van den Berghe,Ida J. van der Klei,Wouter G. van Doorn,Linda F. van Dyk,Marjolein van Egmond,Leo A. van Grunsven,Peter Vandenabeele,Wim Vandenberghe,Ilse Vanhorebeek,Eva C. Vaquero,Guillermo Velasco,Tibor Vellai,Jose Miguel Vicencio,Richard D. Vierstra,Miquel Vila,Cécile Vindis,Cécile Vindis,Giampietro Viola,Maria Teresa Viscomi,Olga V. Voitsekhovskaja,Clarissa von Haefen,Marcela Votruba,Keiji Wada,Richard Wade-Martins,Cheryl L. Walker,Craig M. Walsh,Jochen Walter,Xiang Bo Wan,Aimin Wang,Chenguang Wang,Dawei Wang,Fan Wang,Fen Wang,Guanghui Wang,Haichao Wang,Hong Gang Wang,Horng-Dar Wang,Jin Wang,Ke Wang,Mei Wang,Richard C. Wang,Xinglong Wang,Xuejun Wang,Ying Jan Wang,Yipeng Wang,Zhen Wang,Zhigang Charles Wang,Zhi-Nong Wang,Derick G. Wansink,Diane M. Ward,Hirotaka Watada,Sarah Waters,Paul Webster,Lixin Wei,Conrad C. Weihl,William A. Weiss,Scott M. Welford,Longping Wen,Caroline A. Whitehouse,J. Lindsay Whitton,Alexander J. Whitworth,Thomas Wileman,John W. Wiley,Simon Wilkinson,Dieter Willbold,Roger L. Williams,Peter R. Williamson,Bradly G. Wouters,Chenghan Wu,Dao Cheng Wu,William K.K. Wu,Andreas Wyttenbach,Ramnik J. Xavier,Zhijun Xi,Pu Xia,Gengfu Xiao,Zhiping Xie,Zhonglin Xie,Da Zhi Xu,Jianzhen Xu,Liang Xu,Xiaolei Xu,Ai Yamamoto,Akitsugu Yamamoto,Shunhei Yamashina,Michiaki Yamashita,Xianghua Yan,Mitsuhiro Yanagida,Dun-Sheng Yang,Elizabeth Yang,Jin Ming Yang,Shi Yu Yang,Wannian Yang,Wei Yuan Yang,Zhifen Yang,Meng-Chao Yao,Tso-Pang Yao,Behzad Yeganeh,Wei Lien Yen,Jia Jing Yin,Xiao Ming Yin,Ook Joon Yoo,Gyesoon Yoon,Seung Yong Yoon,Tomohiro Yorimitsu,Yuko Yoshikawa,Tamotsu Yoshimori,Kohki Yoshimoto,Ho Jin You,Richard J. Youle,Anas Younes,Li Yu,Long Yu,Seong-Woon Yu,Wai Haung Yu,Zhi-Min Yuan,Zhenyu Yue,Cheol-Heui Yun,Michisuke Yuzaki,Olga Zabirnyk,Elaine Silva-Zacarin,E. David Zacks,Ldad Zacksenhaus,Nadia Zaffaroni,Zahra Zakeri,Herbert J. Zeh,Scott Zeitlin,Hong Zhang,Hui Ling Zhang,Jianhua Zhang,Jing Pu Zhang,Lin Zhang,Long Zhang,Ming Yong Zhang,Xudong Zhang,Mantong Zhao,Yi Fang Zhao,Ying Zhao,Zhizhuang J. Zhao,Xiaoxiang Zheng,Boris Zhivotovsky,Qing Zhong,Cong Zhao Zhou,Changlian Zhu,Wei-Guo Zhu,Xiao Feng Zhu,Xiongwei Zhu,Yuangang Zhu,Teresa Zoladek,Wei-Xing Zong,Antonio Zorzano,Jürgen Zschocke,Brian S. Zuckerbraun +1287 more
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Journal ArticleDOI
High frequency of mutations of the PIK3CA gene in human cancers
Yardena Samuels,Zhenghe Wang,Alberto Bardelli,Natalie Silliman,Janine Ptak,Steve Szabo,Hai Yan,Adi F. Gazdar,Steven M. Powell,Gregory J. Riggins,James K V Willson,Sanford D. Markowitz,Kenneth W. Kinzler,Bert Vogelstein,Victor E. Velculescu +14 more
TL;DR: To determine if PI3Ks are genetically altered in tumorigenesis, they were sequenced in human for the first time and the results allowed us to assess the importance of phosphatidylinositol 3-kinases in neoplasia.
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