Fine-tuning of MEK signaling is pivotal for limiting B and T cell activation.
Alleles
Animals
B-Lymphocytes
/ metabolism
Female
Humans
Lymphocyte Activation
/ genetics
MAP Kinase Kinase 1
/ metabolism
MAP Kinase Kinase 2
/ genetics
MAP Kinase Signaling System
/ genetics
Male
Mice
Mice, 129 Strain
Mitogen-Activated Protein Kinase 1
/ metabolism
Phosphorylation
Signal Transduction
/ physiology
T-Lymphocytes
/ metabolism
B and T cell activation
Lupus-like disease
Mek
autoimmune disease
autoimmunity
glomerulonephritis
lymphopoiesis
lymphoproliferative disorders
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
11 01 2022
11 01 2022
Historique:
received:
20
12
2020
revised:
05
10
2021
accepted:
15
12
2021
entrez:
12
1
2022
pubmed:
13
1
2022
medline:
15
2
2022
Statut:
ppublish
Résumé
MEK1 and MEK2, the only known activators of ERK, are attractive therapeutic candidates for both cancer and autoimmune diseases. However, how MEK signaling finely regulates immune cell activation is only partially understood. To address this question, we specifically delete Mek1 in hematopoietic cells in the Mek2 null background. Characterization of an allelic series of Mek mutants reveals the presence of distinct degrees of spontaneous B cell activation, which are inversely proportional to the levels of MEK proteins and ERK activation. While Mek1 and Mek2 null mutants have a normal lifespan, 1Mek1 and 1Mek2 mutants retaining only one functional Mek1 or Mek2 allele in hematopoietic cell lineages die from glomerulonephritis and lymphoproliferative disorders, respectively. This establishes that the fine-tuning of the ERK/MAPK pathway is critical to regulate B and T cell activation and function and that each MEK isoform plays distinct roles during lymphocyte activation and disease development.
Identifiants
pubmed: 35021072
pii: S2211-1247(21)01727-7
doi: 10.1016/j.celrep.2021.110223
pii:
doi:
Substances chimiques
Mitogen-Activated Protein Kinase 1
EC 2.7.11.24
MAP Kinase Kinase 1
EC 2.7.12.2
MAP Kinase Kinase 2
EC 2.7.12.2
Map2k1 protein, mouse
EC 2.7.12.2
Map2k2 protein, mouse
EC 2.7.12.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110223Subventions
Organisme : CIHR
ID : MOP-97801
Pays : Canada
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.