Identification of key features required for efficient S-acylation and plasma membrane targeting of sprouty-2.
J Cell Sci
; 133(21)2020 11 05.
Article
en En
| MEDLINE
| ID: mdl-33037124
ABSTRACT
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.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Aciltransferasas
/
Cisteína
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article