Regulation of ERK2 activity by dynamic S-acylation
Summary: Extracellular signal-regulated kinases (ERK1/2) are key effector proteins of the mitogen-activated protein kinase pathway, choreographing essential processes of cellular physiology. Here, we discover that ERK1/2 are subject to S-acylation, a reversible lipid modification of cysteine residue...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723011476 |
| _version_ | 1797682863292809216 |
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| author | Saara-Anne Azizi Tian Qiu Noah E. Brookes Bryan C. Dickinson |
| author_facet | Saara-Anne Azizi Tian Qiu Noah E. Brookes Bryan C. Dickinson |
| author_sort | Saara-Anne Azizi |
| collection | DOAJ |
| description | Summary: Extracellular signal-regulated kinases (ERK1/2) are key effector proteins of the mitogen-activated protein kinase pathway, choreographing essential processes of cellular physiology. Here, we discover that ERK1/2 are subject to S-acylation, a reversible lipid modification of cysteine residues, at C271/C254. The levels of ERK1/2 S-acylation are modulated by epidermal growth factor (EGF) signaling, mirroring its phosphorylation dynamics, and acylation-deficient ERK2 displays altered phosphorylation patterns. We show that ERK1/2 S-acylation is mediated by “writer” protein acyl transferases (PATs) and “eraser” acyl protein thioesterases (APTs) and that chemical inhibition of either lipid addition or removal alters ERK1/2’s EGF-triggered transcriptional program. Finally, in a mouse model of metabolic syndrome, we find that ERK1/2 lipidation levels correlate with alterations in ERK1/2 lipidation writer/eraser expression, solidifying a link between ERK1/2 activity, ERK1/2 lipidation, and organismal health. This study describes how lipidation regulates ERK1/2 and offers insight into the role of dynamic S-acylation in cell signaling more broadly. |
| first_indexed | 2024-03-12T00:06:03Z |
| format | Article |
| id | doaj.art-4ed335a66de445fa9add634cff2a6477 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T00:06:03Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4ed335a66de445fa9add634cff2a64772023-09-17T04:56:06ZengElsevierCell Reports2211-12472023-09-01429113135Regulation of ERK2 activity by dynamic S-acylationSaara-Anne Azizi0Tian Qiu1Noah E. Brookes2Bryan C. Dickinson3Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Medical Scientist Training Program, Pritzker School of Medicine, The University of Chicago, Chicago, IL 60637, USADepartment of Chemistry, The University of Chicago, Chicago, IL 60637, USADepartment of Chemistry, The University of Chicago, Chicago, IL 60637, USADepartment of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Corresponding authorSummary: Extracellular signal-regulated kinases (ERK1/2) are key effector proteins of the mitogen-activated protein kinase pathway, choreographing essential processes of cellular physiology. Here, we discover that ERK1/2 are subject to S-acylation, a reversible lipid modification of cysteine residues, at C271/C254. The levels of ERK1/2 S-acylation are modulated by epidermal growth factor (EGF) signaling, mirroring its phosphorylation dynamics, and acylation-deficient ERK2 displays altered phosphorylation patterns. We show that ERK1/2 S-acylation is mediated by “writer” protein acyl transferases (PATs) and “eraser” acyl protein thioesterases (APTs) and that chemical inhibition of either lipid addition or removal alters ERK1/2’s EGF-triggered transcriptional program. Finally, in a mouse model of metabolic syndrome, we find that ERK1/2 lipidation levels correlate with alterations in ERK1/2 lipidation writer/eraser expression, solidifying a link between ERK1/2 activity, ERK1/2 lipidation, and organismal health. This study describes how lipidation regulates ERK1/2 and offers insight into the role of dynamic S-acylation in cell signaling more broadly.http://www.sciencedirect.com/science/article/pii/S2211124723011476CP: Molecular biology |
| spellingShingle | Saara-Anne Azizi Tian Qiu Noah E. Brookes Bryan C. Dickinson Regulation of ERK2 activity by dynamic S-acylation Cell Reports CP: Molecular biology |
| title | Regulation of ERK2 activity by dynamic S-acylation |
| title_full | Regulation of ERK2 activity by dynamic S-acylation |
| title_fullStr | Regulation of ERK2 activity by dynamic S-acylation |
| title_full_unstemmed | Regulation of ERK2 activity by dynamic S-acylation |
| title_short | Regulation of ERK2 activity by dynamic S-acylation |
| title_sort | regulation of erk2 activity by dynamic s acylation |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723011476 |
| work_keys_str_mv | AT saaraanneazizi regulationoferk2activitybydynamicsacylation AT tianqiu regulationoferk2activitybydynamicsacylation AT noahebrookes regulationoferk2activitybydynamicsacylation AT bryancdickinson regulationoferk2activitybydynamicsacylation |