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.
BCR-ABL
CLL
PI3K signaling
PTEN
RHOA
SLP65
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
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
842340Informations 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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