Citations 2
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.
Extensive polymorphism surrounding the murine Ia A beta chain gene.
Robinson, Randy , Germain, Ronald N. , McKean, D J, Mescher, M F, Seidman, J.G., Seidman, Jonathan G. , Seidman, Jonathan G
The Journal of Immunology | December 31, 2022 | Volume: 131 | Issue: 4 | Pages: 2025-2031
Abstract A segment of the murine immune response-associated (Ia) antigen A beta chain mRNA has been cloned, and this cDNA clone has been used to examine the organization of the genes encoding these highly polymorphic cell surface proteins. To isolate this clone, pIA beta-1, we screened 5000 cDNA clones by a filter hybridization-selection assay using a rabbit heteroantiserum to identify the A beta chain produced in in vitro translation reactions. This clone corresponds to a segment of the mRNA encoding the beta chain of the murine I-A antigen. The 464 bp nucleotide sequence of the insert is consistent with a cDNA clone encoding the carboxyl end of the murine A beta chain. Comparison of this nucleotide sequence to a human Ia beta chain-derived cDNA clone suggests that the two clones could encode proteins that are about 90% homologous in this region. Southern blot analysis using pIA beta-1 as a probe to investigate the structure of the A beta chain gene in inbred strains of mice allows two conclusions. First, there is only one A beta chain gene homologous to this cDNA clone in each haploid mouse genome. Second, the restriction fragments encoding this gene are highly polymorphic. We postulate that the mechanism which generates polymorphic variation of the A beta chain may be involved in generating the restriction site polymorphism within or near the A beta chain gene.