The Small GTPase RHOA Links SLP65 Activation to PTEN Function in Pre B Cells and Is Essential for the Generation and Survival of Normal and Malignant B Cells.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 23 12 2021
accepted: 18 02 2022
entrez: 4 4 2022
pubmed: 5 4 2022
medline: 9 4 2022
Statut: epublish

Résumé

The generation, differentiation, survival and activation of B cells are coordinated by signals emerging from the B cell antigen receptor (BCR) or its precursor, the pre-BCR. The adaptor protein SLP65 (also known as BLNK) is an important signaling factor that controls pre-B cell differentiation by down-regulation of PI3K signaling. Here, we investigated the mechanism by which SLP65 interferes with PI3K signaling. We found that SLP65 induces the activity of the small GTPase RHOA, which activates PTEN, a negative regulator of PI3K signaling, by enabling its translocation to the plasma membrane. The essential role of RHOA is confirmed by the complete block in early B cell development in conditional

Identifiants

pubmed: 35371049
doi: 10.3389/fimmu.2022.842340
pmc: PMC8965026
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Receptors, Antigen, B-Cell 0
Monomeric GTP-Binding Proteins EC 3.6.5.2
RhoA protein, mouse EC 3.6.5.2
rhoA GTP-Binding Protein EC 3.6.5.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

842340

Informations de copyright

Copyright © 2022 Vadakumchery, Faraidun, Ayoubi, Outaleb, Schmid, Abdelrasoul, Amendt, Khadour, Setz, Göhring, Lodd, Hitzing, Alkhatib, Bilal, Benckendorff, Al Shugri, Brakebusch, Engels, Datta, Hobeika, Alsadeq and Jumaa.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Anila Vadakumchery (A)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Hemin Faraidun (H)

Department of Molecular Immunology, Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.

Omar El Ayoubi (OE)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Issame Outaleb (I)

Department of Molecular Immunology, Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.

Vera Schmid (V)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Hend Abdelrasoul (H)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Timm Amendt (T)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Ahmad Khadour (A)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Corinna Setz (C)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Katharina Göhring (K)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Karoline Lodd (K)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Christoffer Hitzing (C)

Institute of Cellular & Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.

Alabbas Alkhatib (A)

Department of Molecular Immunology, Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.

Mayas Bilal (M)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Julian Benckendorff (J)

Institute of Pathology, Ulm University Medical Center, Ulm, Germany.

Abdul Kader Al Shugri (AK)

Institute of Pathology, Ulm University Medical Center, Ulm, Germany.

Cord Herbert Brakebusch (CH)

Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.

Niklas Engels (N)

Institute of Cellular & Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.

Moumita Datta (M)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Elias Hobeika (E)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Ameera Alsadeq (A)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.

Hassan Jumaa (H)

Institute of Immunology, Ulm University Medical Center, Ulm, Germany.
Department of Molecular Immunology, Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.

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