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

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

doi:10.1126/science.add8947

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

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

Hyoungjun Ham, Huie Jing, Ian Lamborn, Megan Kober, Alexey Koval, Yamina Berchiche, D. Eric Anderson, Kirk Druey, Judith Mandl, Bertrand Isidor, …

Science (American Association for the Advancement of Science), Vol.385(6715), p.1314

20/09/2024

DOI: https://doi.org/10.1126/science.add8947

PMID: 39298586

Résumé

Cell Movement

Cell Proliferation

Germ-Line Mutation

GTP-Binding Protein alpha Subunit, Gi2

Human health and pathology

Humans

Immunity

Life Sciences

MAP Kinase Signaling System

Pedigree

Phosphatidylinositol 3-Kinases

Proto-Oncogene Proteins c-akt

ras GTPase-Activating Proteins

ras Proteins

Receptors, Antigen, T-Cell

Signal Transduction

T-Lymphocytes

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.

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Titre: Germline mutations in a G protein identify signaling cross-talk in T cells
Créateurs - sans rôle: Hyoungjun Ham - Laboratory of Clinical Immunology and Microbiology [Bethesda, MA, USA]
Huie Jing - Laboratory of Clinical Immunology and Microbiology [Bethesda, MA, USA]
Ian Lamborn - Laboratory of Clinical Immunology and Microbiology [Bethesda, MA, USA]
Megan Kober - Laboratory of Clinical Immunology and Microbiology [Bethesda, MA, USA]
Alexey Koval - Université de Genève = University of Geneva
Yamina Berchiche - Rockefeller University [New York]
D. Eric Anderson - Laboratory of Biological Modeling
Kirk Druey - National Institute of Allergy and Infectious Diseases [Bethesda]
Judith Mandl - National Institute of Allergy and Infectious Diseases [Bethesda]
Bertrand Isidor - Hôtel-Dieu de Nantes
Carlos Ferreira - National Human Genome Research Institute
Alexandra Freeman - National Institutes of Health [Bethesda, MD, USA]
Sundar Ganesan - National Institutes of Health [Bethesda, MD, USA]
Meliha Karsak - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
Peter Mustillo - Nationwide Children's Hospital
Juliana Teo - Children's Hospital [Westmead, Australia]
Zarazuela Zolkipli-Cunningham - Children’s Hospital of Philadelphia
Nicolas Chatron - Centre Hospitalier Lyon Sud [CHU - HCL]
François Lecoquierre - UNIROUEN - UFR Santé
Andrew Oler - National Institute of Allergy and Infectious Diseases [Bethesda]
Jana Pachlopnik Schmid - University of Zurich
Douglas Kuhns - Frederick National Laboratory for Cancer Research
Xuehua Xu - National Institute of Allergy and Infectious Diseases [Bethesda]
Fabian Hauck - Fakultät für Physik - Ludwig-Maximilians-Universität [München/Munich]
Waleed Al-Herz - Kuwait University
Matias Wagner - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
Paulien Terhal - University Medical Center [Utrecht]
Mari Muurinen - Folkhälsan Research Center
Vincent Barlogis - Hôpital de la Timone [CHU - APHM]
Phillip Cruz - National Institute of Allergy and Infectious Diseases [Bethesda]
Jeffrey Danielson - National Institute of Allergy and Infectious Diseases
Helen Stewart - Oxford University Hospitals NHS Trust
Petra Loid - Folkhälsan Research Center
Sebastian Rading - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
Boris Keren - Assistance Publique – Hôpitaux de Paris
Rolph Pfundt - Donders Institute for Brain, Cognition and Behaviour
Kol Zarember - National Institute of Allergy and Infectious Diseases [Bethesda]
Katharina Vill - University Hospital LMU Munich
Lorraine Potocki - Baylor College of Medicine
Kenneth Olivier - National Heart, Lung, and Blood Institute [Bethesda]
Gaetan Lesca - Hospices Civils de Lyon
Laurence Faivre - Génétique des anomalies du développement (CTM UMR 1231)
Melanie Wong - Children's Hospital [Westmead, Australia]
Anne Puel - Rockefeller University [New York]
Janet Chou - Harvard Medical School [Boston]
Maud Tusseau - Hospices Civils de Lyon
Niki Moutsopoulos - National Institute of Health
Helen Matthews - National Institute of Allergy and Infectious Diseases [Bethesda]
Cas Simons - Garvan Institute of medical research
Ryan Taft - The University of Queensland
Ariane Soldatos - National Institute of Neurological Disorders and Stroke
Etienne Masle-Farquhar - UNSW Faculty of Medicine [Sydney]
Stefania Pittaluga - National Cancer Institute [Bethesda]
Robert Brink - St. Vincent’s Clinical School [Sydney, Australia]
Danielle Fink - Frederick National Laboratory for Cancer Research
Heidi Kong - National Institute of Health
Juraj Kabat - National Institute of Allergy and Infectious Diseases [Bethesda]
Woo Sung Kim - National Institute of Allergy and Infectious Diseases [Bethesda]
Tatjana Bierhals - University Medical Center Hamburg-Eppendorf
Kazuyuki Meguro - National Human Genome Research Institute
Amy Hsu - National Institute of Allergy and Infectious Diseases [Bethesda]
Jingwen Gu - National Institute of Allergy and Infectious Diseases [Bethesda]
Jennifer Stoddard - National Institute of Health
Benito Banos-Pinero - Oxford University Hospitals NHS Trust
Maria Slack - University of Rochester Medical Center
Giampaolo Trivellin - Eunice Kennedy Shriver National Institute of Child Health and Human Development
Benoît Mazel - Centre de référence des maladies rares des déficiences intellectuelles de causes rares (CHU Dijon)
Maarja Soomann - University Children’s Hospital Zurich
Samuel Li - National Institute of Allergy and Infectious Diseases [Bethesda]
Val Watts - Purdue University [West Lafayette]
Constantine Stratakis - Eunice Kennedy Shriver National Institute of Child Health and Human Development
Maria Rodriguez-Quevedo - Schulze Center for Novel Therapeutics, Division of Oncology Research [Rochester]
Ange-Line Bruel - Génétique des anomalies du développement (CTM UMR 1231)
Marita Lipsanen-Nyman - Helsinki University Hospital [Finland]
Paul Saultier - Hôpital de la Timone [CHU - APHM]
Rashmi Jain - Oxford University Hospitals NHS Trust
Daphne Lehalle - CHU Trousseau [APHP]
Daniel Torres - National Institute of Allergy and Infectious Diseases [Bethesda]
Kathleen Sullivan - Children’s Hospital of Philadelphia
Sébastien Barbarot - Physiopathologie des Adaptations Nutritionnelles
Axel Neu - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
Yannis Duffourd - Génétique des anomalies du développement (CTM UMR 1231)
Morgan Similuk - National Institute of Allergy and Infectious Diseases
Kirsty Mcwalter - GeneDx [Gaithersburg, MD, USA]
Pierre Blanc - Laboratoire de Biologie Médicale SeqOIA [Paris]
Stéphane Bézieau - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
Tian Jin - National Institute of Allergy and Infectious Diseases [Bethesda]
Raif Geha - Harvard Medical School
Jean-Laurent Casanova - Rockefeller University [New York]
Outi Makitie - Folkhälsan Research Center
Christian Kubisch - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
Patrick Edery - Hospices Civils de Lyon
John Christodoulou - The University of Melbourne
Ronald Germain - National Institute of Allergy and Infectious Diseases [Bethesda]
Christopher Goodnow - Garvan Institute of medical research
Thomas Sakmar - Karolinska Institutet [Stockholm]
Daniel Billadeau - Schulze Center for Novel Therapeutics, Division of Oncology Research [Rochester]
Sébastien Küry - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
Vladimir Katanaev - Université de Genève = University of Geneva
Yu Zhang - National Institute of Allergy and Infectious Diseases [Bethesda]
Détails de publication: Science (American Association for the Advancement of Science), Vol.385(6715), p.1314
Éditeur: American Association for the Advancement of Science (AAAS)
Identifiants: 99155842609311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article