Mazel, Benoît
Mayo Clinic
Centre de Génétique et Centre de Référence "Anomalies du Développement et Syndromes Malformatifs de l'Inter-région Est", FHU TRANSLAD, CHU Dijon Bourgogne, Dijon, France.
Citations 1
Germline mutations in a G protein identify signaling cross-talk in T cells
Ham, Hyoungjun , Jing, Huie , Lamborn, Ian T. , Kober, M. , Anderson, David E. , Druey, Kirk M. , Mandl, Judith N. , Isidor, Bertrand , Freeman, Alexandra F. , Ganesan, Sundar , Karsak, Meliha , Mustillo, Peter , Teo, Juliana , Zolkipli‐Cunningham, Zarazuela , Lecoquierre, François , Schmid, Jana Pachlopnik , Kuhns, Douglas B. , Xu, Xuehua , Al–Herz, Waleed , Terhal, Paulien A., Muurinen, Mari , Barlogis, Vincent , Danielson, Jeffrey J. , Stewart, Helen , Rading, Sebastian, Keren, Boris , Pfundt, Rolph , Potocki, Lorraine , Olivier, Kenneth N., Faivre, Laurence , Wong, Melanie , Puel, Anne , Chou, Janet , Tusseau, Maud, Moutsopoulos, Niki M. , Matthews, Helen, Simons, Cas , Fink, Danielle , Kong, Heidi H. , Kabát, Juraj , Kim, Woo Sung , Bierhals, Tatjana , Meguro, Kazuyuki , Gu, Jingwen , Stoddard, Jennifer , Banos-Pinero, Benito, Slack, Maria A., Trivellin, Giampaolo , Mazel, Benoît , Li, Samuel T. , Watts, Val J. , Rodriguez-Quevedo, Maria F. , Bruel, Ange‐Line , Lehalle, Daphné , Torres, Daniel , Sullivan, Kathleen E. , Duffourd, Yannis, Similuk, Morgan , Blanc, Pierre , Jin, Tian, Geha, Raif S., Casanova, Jean‐Laurent , Mäkitie, Outi , Edery, Patrick , Germain, Ronald N. , Billadeau, Daniel D. , Zhang, Yu , Lenardo, Michael J. , Kober, Megan M , Koval, Alexey , Anderson, D Eric , Druey, Kirk M , Mandl, Judith N , Isidor, Bertrand , Ferreira, Carlos R , Freeman, Alexandra F , Karsak, Meliha , Mustillo, Peter J , Teo, Juliana , Chatron, Nicolas , Lecoquierre, Francois , 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 , Loid, Petra , Keren, Boris , Pfundt, Rolph , Zarember, Kol A , Vill, Katharina , Olivier, Kenneth N , Lesca, Gaetan , Faivre, Laurence , Puel, Anne , Chou, Janet , Moutsopoulos, Niki M , Simons, Cas , Soldatos, Ariane , Masle-Farquhar, Etienne , Pittaluga, Stefania , Brink, Robert , Kong, Heidi H , Kabat, Juraj , Bierhals, Tatjana , Hsu, Amy P. , Gu, Jingwen , 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 , Lehalle, Daphne , Torres, Daniel , Barbarot, Sébastien , Neu, Axel , Similuk, Morgan N , McWalter, Kirsty , Blanc, Pierre , Bézieau, Stéphane , Geha, Raif S , Casanova, Jean Laurent , Makitie, Outi M , Edery, Patrick , Christodoulou, John , Germain, Ronald N , Goodnow, Christopher C , Sakmar, Thomas P , Billadeau, Daniel D , Kury, Sebastien , Katanaev, Vladimir L , Zhang, Yu , Lenardo, Michael J , Su, Helen C , Berchiche, Yamina A. , Wagner, Matias , Cruz, Phillip , Lesca, Gaëtan , Tusseau, Maud , Taft, Ryan J. , Pittaluga, Stefania , Baños-Piñero, Benito, Stratakis, Constantine A. , Jain, Rashmi, Bezieau, Stéphane , Jin, Tian , Kubisch, Christian , Küry, Sébastien , Su, Helen C.
Science | September 19, 2024 | Volume: 385 | Issue: 6715 | Pages: No page available
Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase–mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G αi2 mutations had clinical presentations that included impaired immunity. Mutant G αi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G αi2 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.