Identification of key features required for efficient S-acylation and plasma membrane targeting of Sprouty-2

Carolina Locatelli, Kimon Lemonidis, Christine Salaun, Nicholas C. O. Tomkinson, Luke H. Chamberlain

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
4 Downloads (Pure)


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 cysteines 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 cysteines-265/268 were identified as key targets of this enzyme. In contrast, the low specificity/high activity zDHHC3/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 alpha 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.
Original languageEnglish
Article numberjcs249664
Number of pages16
JournalJournal of Cell Science
Issue number21
Early online date5 Nov 2020
Publication statusE-pub ahead of print - 5 Nov 2020


  • Sprouty-2
  • post-translational modification (PTM)
  • protein S-acylation
  • zDHHC enzymes


Dive into the research topics of 'Identification of key features required for efficient S-acylation and plasma membrane targeting of Sprouty-2'. Together they form a unique fingerprint.

Cite this