Ligand requirements for immunoreceptor triggering.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
13 Sep 2024
13 Sep 2024
Historique:
received:
10
01
2024
accepted:
30
08
2024
medline:
14
9
2024
pubmed:
14
9
2024
entrez:
13
9
2024
Statut:
epublish
Résumé
Leukocytes interact with other cells using cell surface receptors. The largest group of such receptors are non-catalytic tyrosine phosphorylated receptors (NTRs), also called immunoreceptors. NTR signalling requires phosphorylation of cytoplasmic tyrosine residues by SRC-family tyrosine kinases. How ligand binding to NTRs induces this phosphorylation, also called NTR triggering, remains controversial, with roles suggested for size-based segregation, clustering, and mechanical force. Here we exploit a recently developed cell-surface generic ligand system to explore the ligand requirements for NTR triggering. We examine the effect of varying the ligand's length, mobility and valency on the activation of representative members of four NTR families: SIRPβ1, Siglec 14, NKp44 and TREM-1. Increasing the ligand length impairs activation via NTRs, despite enhancing cell-cell conjugation, while varying ligand mobility has little effect on either conjugation or activation. Increasing the valency of the ligand, while enhancing cell-cell conjugation, does not enhance activation at equivalent levels of conjugation. These findings are more consistent with a role for size-based segregation, rather than mechanical force or clustering, in NTR triggering, suggesting a role for the kinetic-segregation model.
Identifiants
pubmed: 39271744
doi: 10.1038/s42003-024-06817-y
pii: 10.1038/s42003-024-06817-y
doi:
Substances chimiques
Ligands
0
Receptors, Immunologic
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1138Subventions
Organisme : Wellcome Trust (Wellcome)
ID : 101799/Z/13/Z
Informations de copyright
© 2024. The Author(s).
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