Activation of the PDGF β Receptor by a Persistent Artificial Signal Peptide.
Amino Acid Sequence
Animals
B-Lymphocytes
/ cytology
Cell Line
Cell Proliferation
/ drug effects
Gene Expression
Glycosylation
Hydrophobic and Hydrophilic Interactions
Interleukin-3
/ pharmacology
Mice
Mutation
Protein Engineering
/ methods
Protein Sorting Signals
/ genetics
Receptor, Platelet-Derived Growth Factor beta
/ chemistry
Signal Transduction
/ genetics
Structure-Activity Relationship
E5 protein
Receptor tyrosine kinase
Transmembrane domain
Transmembrane protein
Traptamer
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
15 10 2021
15 10 2021
Historique:
received:
28
05
2021
revised:
25
07
2021
accepted:
26
08
2021
pubmed:
3
9
2021
medline:
25
11
2021
entrez:
2
9
2021
Statut:
ppublish
Résumé
Most eukaryotic transmembrane and secreted proteins contain N-terminal signal peptides that mediate insertion of the nascent translation products into the membrane of the endoplasmic reticulum. After membrane insertion, signal peptides typically are cleaved from the mature protein and degraded. Here, we tested whether a small hydrophobic protein selected for growth promoting activity in mammalian cells retained transforming activity while also acting as a signal peptide. We replaced the signal peptide of the PDGF β receptor (PDGFβR) with a previously described 29-residue artificial transmembrane protein named 9C3 that can activate the PDGFβR in trans. We showed that a modified version of 9C3 at the N-terminus of the PDGFβR can function as a signal peptide, as assessed by its ability to support high level expression, glycosylation, and cell surface localization of the PDGFβR. The 9C3 signal peptide retains its ability to interact with the transmembrane domain of the PDGFβR and cause receptor activation and cell proliferation. Cleavage of the 9C3 signal peptide from the mature receptor is not required for these activities. However, signal peptide cleavage does occur in some molecules, and the cleaved signal peptide can persist in cells and activate a co-expressed PDGFβR in trans. Our finding that a hydrophobic sequence can display signal peptide and transforming activity suggest that some naturally occurring signal peptides may also display additional biological activities by interacting with the transmembrane domains of target proteins.
Identifiants
pubmed: 34474086
pii: S0022-2836(21)00456-3
doi: 10.1016/j.jmb.2021.167223
pmc: PMC8530902
mid: NIHMS1741974
pii:
doi:
Substances chimiques
Interleukin-3
0
Protein Sorting Signals
0
Receptor, Platelet-Derived Growth Factor beta
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
167223Subventions
Organisme : NCI NIH HHS
ID : R01 CA037157
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA037157
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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