Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1)
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. AKT dephosphorylation and autophagy are associated with DM1. Autophagy has been widely studied in DM1, although the endocytic pathway has not. AKT has a critical role in endocytosis, and its phosphorylation is mediated by the activation of tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR). EGF-activated EGFR triggers the internalization and degradation of ligand-receptor complexes that serve as a PI3K/AKT signaling platform. Here, we used primary fibroblasts from healthy subjects and DM1 patients. DM1-derived fibroblasts showed increased autophagy flux, with enlarged endosomes and lysosomes. Thereafter, cells were stimulated with a high concentration of EGF to promote EGFR internalization and degradation. Interestingly, EGF binding to EGFR was reduced in DM1 cells and EGFR internalization was also slowed during the early steps of endocytosis. However, EGF-activated EGFR enhanced AKT and ERK1/2 phosphorylation levels in the DM1-derived fibroblasts. Therefore, there was a delay in EGF-stimulated EGFR endocytosis in DM1 cells; this alteration might be due to the decrease in the binding of EGF to EGFR, and not to a decrease in AKT phosphorylation.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
---|---|
Enthalten in: |
Cells - 11(2022), 19 vom: 27. Sept. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Alegre-Cortés, Eva [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 17.10.2022 Date Revised 02.12.2022 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.3390/cells11193018 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM347460437 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM347460437 | ||
003 | DE-627 | ||
005 | 20231226033900.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/cells11193018 |2 doi | |
028 | 5 | 2 | |a pubmed24n1158.xml |
035 | |a (DE-627)NLM347460437 | ||
035 | |a (NLM)36230978 | ||
035 | |a (PII)3018 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Alegre-Cortés, Eva |e verfasserin |4 aut | |
245 | 1 | 0 | |a Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 17.10.2022 | ||
500 | |a Date Revised 02.12.2022 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. AKT dephosphorylation and autophagy are associated with DM1. Autophagy has been widely studied in DM1, although the endocytic pathway has not. AKT has a critical role in endocytosis, and its phosphorylation is mediated by the activation of tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR). EGF-activated EGFR triggers the internalization and degradation of ligand-receptor complexes that serve as a PI3K/AKT signaling platform. Here, we used primary fibroblasts from healthy subjects and DM1 patients. DM1-derived fibroblasts showed increased autophagy flux, with enlarged endosomes and lysosomes. Thereafter, cells were stimulated with a high concentration of EGF to promote EGFR internalization and degradation. Interestingly, EGF binding to EGFR was reduced in DM1 cells and EGFR internalization was also slowed during the early steps of endocytosis. However, EGF-activated EGFR enhanced AKT and ERK1/2 phosphorylation levels in the DM1-derived fibroblasts. Therefore, there was a delay in EGF-stimulated EGFR endocytosis in DM1 cells; this alteration might be due to the decrease in the binding of EGF to EGFR, and not to a decrease in AKT phosphorylation | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a AKT | |
650 | 4 | |a DMPK | |
650 | 4 | |a LBPA | |
650 | 4 | |a autophagy | |
650 | 4 | |a endosomes | |
650 | 4 | |a lysosomes | |
650 | 4 | |a muscle atrophy | |
650 | 7 | |a 3' Untranslated Regions |2 NLM | |
650 | 7 | |a Ligands |2 NLM | |
650 | 7 | |a Epidermal Growth Factor |2 NLM | |
650 | 7 | |a 62229-50-9 |2 NLM | |
650 | 7 | |a EGFR protein, human |2 NLM | |
650 | 7 | |a EC 2.7.10.1 |2 NLM | |
650 | 7 | |a ErbB Receptors |2 NLM | |
650 | 7 | |a EC 2.7.10.1 |2 NLM | |
650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
700 | 1 | |a Giménez-Bejarano, Alberto |e verfasserin |4 aut | |
700 | 1 | |a Uribe-Carretero, Elisabet |e verfasserin |4 aut | |
700 | 1 | |a Paredes-Barquero, Marta |e verfasserin |4 aut | |
700 | 1 | |a Marques, André R A |e verfasserin |4 aut | |
700 | 1 | |a Lopes-da-Silva, Mafalda |e verfasserin |4 aut | |
700 | 1 | |a Vieira, Otília V |e verfasserin |4 aut | |
700 | 1 | |a Canales-Cortés, Saray |e verfasserin |4 aut | |
700 | 1 | |a Camello, Pedro J |e verfasserin |4 aut | |
700 | 1 | |a Martínez-Chacón, Guadalupe |e verfasserin |4 aut | |
700 | 1 | |a Aiastui, Ana |e verfasserin |4 aut | |
700 | 1 | |a Fernández-Torrón, Roberto |e verfasserin |4 aut | |
700 | 1 | |a López de Munain, Adolfo |e verfasserin |4 aut | |
700 | 1 | |a Gomez-Suaga, Patricia |e verfasserin |4 aut | |
700 | 1 | |a Niso-Santano, Mireia |e verfasserin |4 aut | |
700 | 1 | |a González-Polo, Rosa A |e verfasserin |4 aut | |
700 | 1 | |a Fuentes, José M |e verfasserin |4 aut | |
700 | 1 | |a Yakhine-Diop, Sokhna M S |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cells |d 2011 |g 11(2022), 19 vom: 27. Sept. |w (DE-627)NLM227066421 |x 2073-4409 |7 nnns |
773 | 1 | 8 | |g volume:11 |g year:2022 |g number:19 |g day:27 |g month:09 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/cells11193018 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 11 |j 2022 |e 19 |b 27 |c 09 |