PXD048980-1

PXD048980 is an original dataset announced via ProteomeXchange.

Title	- Identification of Gαi2-interacting proteins via affinity pull-down and quantitative mass-spectrometry analysis.
Description	In studying patients with activating GNAI2 mutations, we observed T cell hyperresponsiveness that was independent of cAMP suppression. Therefore, we hypothesized that Gαi2 utilizes alternative signal transduction pathways which might be delineated by identifying its interacting proteins in T cells. To accomplish this, we performed affinity pulldown followed by quantitative mass-spectrometry analysis. Using this approach, we identified both well-known and previously reported interactors of Gαi2 as well as 128 previously unreported interactors including RASA2. We validated RASA2, a GTPase-activating protein for RAS, and PP2A-A/C as Gαi2 effector targets by several methods: overexpression-coimmunoprecipitations using 293T cells, endogenous coimmunoprecipitations from patient T cells, and by mixing-pulldown experiments using purified recombinant proteins. Additional imaging experiments confirmed Gαi2-RASA2 interactions within living cells and delineated that activating mutations of Gαi2 sequester RASA2 toward the plasma membrane to promote RAS activation for T cell growth and proliferation.
HostingRepository	PRIDE
AnnounceDate	2024-09-20
AnnouncementXML	Submission_2024-09-20_05:00:59.723.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD048980
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	David Anderson
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-29 09:24:35	ID requested
⏵ 1	2024-09-20 05:01:00	announced
2	2024-10-22 06:59:17	announced	2024-10-22: Updated project metadata.

Ham H, Jing H, Lamborn IT, Kober MM, Koval A, Berchiche YA, Anderson DE, Druey KM, Mandl JN, Isidor B, Ferreira CR, Freeman AF, Ganesan S, Karsak M, Mustillo PJ, Teo J, Zolkipli-Cunningham Z, Chatron N, Lecoquierre F, Oler AJ, Schmid JP, Kuhns DB, Xu X, Hauck F, Al-Herz W, Wagner M, Terhal PA, Muurinen M, Barlogis V, Cruz P, Danielson J, Stewart H, Loid P, Rading S, Keren B, Pfundt R, Zarember KA, Vill K, Potocki L, Olivier KN, Lesca G, Faivre L, Wong M, Puel A, Chou J, Tusseau M, Moutsopoulos NM, Matthews HF, Simons C, Taft RJ, Soldatos A, Masle-Farquhar E, Pittaluga S, Brink R, Fink DL, Kong HH, Kabat J, Kim WS, Bierhals T, Meguro K, Hsu AP, Gu J, Stoddard J, Banos-Pinero B, Slack M, Trivellin G, Mazel B, Soomann M, Li S, Watts VJ, Stratakis CA, Rodriguez-Quevedo MF, Bruel AL, Lipsanen-Nyman M, Saultier P, Jain R, Lehalle D, Torres D, Sullivan KE, Barbarot S, Neu A, Duffourd Y, Similuk M, McWalter K, Blanc P, B, é, zieau S, Jin T, Geha RS, Casanova JL, Makitie OM, Kubisch C, Edery P, Christodoulou J, Germain RN, Goodnow CC, Sakmar TP, Billadeau DD, K, ü, ry S, Katanaev VL, Zhang Y, Lenardo MJ, Su HC, Germline mutations in a G protein identify signaling cross-talk in T cells. Science, 385(6715):eadd8947(2024) [pubmed]

10.1126/science.add8947;

10.6019/PXD048980;

submitter keyword: GPCRs, G-protein coupled receptors, GNAI2,- Gαi2, G-protein

Helen C. Su
contact affiliation	Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Department of Health and Human Services, Unites States Government
contact email	hsu@niaid.nih.gov
lab head
David Anderson
contact affiliation	NIH/NIDDK
contact email	davida@mail.nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048980
     1. Label: PRIDE project
     2. Name: - Identification of Gαi2-interacting proteins via affinity pull-down and quantitative mass-spectrometry analysis.