Science (New York, N.Y.) · 2024

Germline mutations in a G protein identify signaling cross-talk in T cells.

СтатьяПоддержка исследования: вне правительства СШАResearch Support, N.I.H., IntramuralПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди

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Ham Hyoungjun, Jing Huie, Lamborn Ian T, Kober Megan M, Koval Alexey, Berchiche Yamina A, Anderson D Eric, Druey Kirk M, Mandl Judith N, Isidor Bertrand, Ferreira Carlos R, Freeman Alexandra F, Ganesan Sundar, Karsak Meliha, Mustillo Peter J, Teo Juliana, Zolkipli-Cunningham Zarazuela, Chatron Nicolas, Lecoquierre François, Oler Andrew J, Schmid Jana Pachlopnik, Kuhns Douglas B, Xu Xuehua, Hauck Fabian, Al-Herz Waleed, Wagner Matias, Terhal Paulien A, Muurinen Mari, Barlogis Vincent, Cruz Phillip, Danielson Jeffrey, Stewart Helen, Loid Petra, Rading Sebastian, Keren Boris, Pfundt Rolph, Zarember Kol A, Vill Katharina, Potocki Lorraine, Olivier Kenneth N, Lesca Gaetan, Faivre Laurence, Wong Melanie, Puel Anne, Chou Janet, Tusseau Maud, Moutsopoulos Niki M, Matthews Helen F, Simons Cas, Taft Ryan J, Soldatos Ariane, Masle-Farquhar Etienne, Pittaluga Stefania, Brink Robert, Fink Danielle L, Kong Heidi H, Kabat Juraj, Kim Woo Sung, Bierhals Tatjana, Meguro Kazuyuki, Hsu Amy P, Gu Jingwen, Stoddard Jennifer, Banos-Pinero Benito, Slack Maria, Trivellin Giampaolo, Mazel Benoît, Soomann Maarja, Li Samuel, Watts Val J, Stratakis Constantine A, Rodriguez-Quevedo Maria F, Bruel Ange-Line, Lipsanen-Nyman Marita, Saultier Paul, Jain Rashmi, Lehalle Daphne, Torres Daniel, Sullivan Kathleen E, Barbarot Sébastien, Neu Axel, Duffourd Yannis, Similuk Morgan, McWalter Kirsty, Blanc Pierre, Bézieau Stéphane, Jin Tian, Geha Raif S, Casanova Jean-Laurent, Makitie Outi M, Kubisch Christian, Edery Patrick, Christodoulou John, Germain Ronald N, Goodnow Christopher C, Sakmar Thomas P, Billadeau Daniel D, Küry Sébastien, Katanaev Vladimir L, Zhang Yu, Lenardo Michael J, Su Helen C

Аннотация

Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2, which encodes Gαi2, a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase-mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating Gαi2 mutations had clinical presentations that included impaired immunity. Mutant Gαi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant Gαi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)-activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-AKT S6 signaling to drive cellular growth and proliferation.

Предметные рубрики MeSH

Humans Cell Movement Cell Proliferation Germ-Line Mutation GTP-Binding Protein alpha Subunit, Gi2 Immunity MAP Kinase Signaling System Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-akt ras GTPase-Activating Proteins ras Proteins Receptors, Antigen, T-Cell Signal Transduction T-Lymphocytes Pedigree

Germline mutations in a G protein identify signaling cross-talk in T cells.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH