Sammanfattning
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.
Originalspråk | engelska |
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Artikelnummer | eadd8947 |
Tidskrift | Science (New York, N.Y.) |
Volym | 385 |
Nummer | 6715 |
Antal sidor | 18 |
ISSN | 0036-8075 |
DOI | |
Status | Publicerad - 20 sep. 2024 |
MoE-publikationstyp | A1 Tidskriftsartikel-refererad |
Vetenskapsgrenar
- 3111 Biomedicinska vetenskaper