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

ABSTRACT: 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 extr

SUBMITTER: Ham H 

PROVIDER: S-EPMC11811912 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature