Identification of key features required for efficient S-acylation and plasma membrane targeting of sprouty-2
| Autor: | Christine Salaün, Luke H. Chamberlain, Carolina Locatelli, Nicholas C. O. Tomkinson, Kimon Lemonidis |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Sprouty-2
ZDHHC enzymes PTM medicine.medical_treatment Acylation Regulator Nerve Tissue Proteins Biology S-acylation 03 medical and health sciences 0302 clinical medicine Palmitoylation medicine Animals Cysteine 030304 developmental biology chemistry.chemical_classification 0303 health sciences Growth factor Cell Membrane Cell Biology QR Cell biology Rats Membrane Signalling Enzyme chemistry 030220 oncology & carcinogenesis Post-translational modification Alpha helix Acyltransferases Research Article |
| Zdroj: | Journal of Cell Science article-version (VoR) Version of Record |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Sprouty-2 is an important regulator of growth factor signalling and a tumour suppressor protein. The defining feature of this protein is a cysteine-rich domain (CRD) that contains twenty-six cysteine residues and is modified by S-acylation. In this study, we show that the CRD of sprouty-2 is differentially modified by S-acyltransferase enzymes. The high specificity/low activity zDHHC17 enzyme mediated restricted S-acylation of sprouty-2, and cysteine-265 and -268 were identified as key targets of this enzyme. In contrast, the low specificity/high activity zDHHC3 and zDHHC7 enzymes mediated more expansive modification of the sprouty-2 CRD. Nevertheless, S-acylation by all enzymes enhanced sprouty-2 expression, suggesting that S-acylation stabilises this protein. In addition, we identified two charged residues (aspartate-214 and lysine-223), present on opposite faces of a predicted α-helix in the CRD, which are essential for S-acylation of sprouty-2. Interestingly, mutations that perturbed S-acylation also led to a loss of plasma membrane localisation of sprouty-2 in PC12 cells. This study provides insight into the mechanisms and outcomes of sprouty-2 S-acylation, and highlights distinct patterns of S-acylation mediated by different classes of zDHHC enzymes. Highlighted Article: S-acylation of the tumour suppressor protein sprouty-2 requires specific cysteine and charged residues in the cysteine-rich domain, and regulates plasma membrane targeting. |
| Databáze: | OpenAIRE |
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