Article: Effect of Serine Phosphorylation and Ser25 Phospho-Mimicking Mutations on Nuclear Localisation and Ligand Interactions of Annexin A2
Journal of Molecular Biology. 2014 June 26, v. 426
2014
Abstract: Annexin A2 (AnxA2) interacts with numerous ligands, including calcium, lipids, mRNAs and intracellular and extracellular proteins. Different post-translational modifications participate in the discrimination of the functions of AnxA2 by modulating its ... ...
| Abstract | Annexin A2 (AnxA2) interacts with numerous ligands, including calcium, lipids, mRNAs and intracellular and extracellular proteins. Different post-translational modifications participate in the discrimination of the functions of AnxA2 by modulating its ligand interactions. Here, phospho-mimicking mutants (AnxA2-S25E and AnxA2-S25D) were employed to investigate the effects of Ser25 phosphorylation on the structure and function of AnxA2 by using AnxA2-S25A as a control. The overall α-helical structure of AnxA2 is not affected by the mutations, since the thermal stabilities and aggregation tendencies of the mutants differ only slightly from the wild-type (wt) protein. Unlike wt AnxA2, all mutants bind the anxA2 3â² untranslated region and β-γ-G-actin with high affinity in a Ca2+-independent manner. AnxA2-S25E is not targeted to the nucleus in transfected PC12 cells. In vitro phosphorylation of AnxA2 by protein kinase C increases its affinity to mRNA and inhibits its nuclear localisation, in accordance with the data obtained with the phospho-mimicking mutants. Ca2+-dependent binding of wt AnxA2 to phosphatidylinositol, phosphatidylinositol-3-phosphate, phosphatidylinositol-4-phosphate and phosphatidylinositol-5-phosphate, as well as weaker but still Ca2+-dependent binding to phosphatidylserine and phosphatidylinositol-3,5-bisphosphate, was demonstrated by a proteinâlipid overlay assay, whereas binding of AnxA2 to these lipids, as well as its binding to liposomes, is inhibited by the Ser25 mutations. Thus, introduction of a modification (mutation or phosphorylation) at Ser25 appears to induce a conformational change leading to increased accessibility of the mRNA- and G-actin-binding sites in domain IV independent of Ca2+ levels, while the Ca2+-dependent binding of AnxA2 to phospholipids is attenuated. |
|---|---|
| Keywords | calcium ; ligands ; messenger RNA ; mutants ; mutation ; phosphatidylserines ; phosphorylation ; post-translational modification ; protein kinase C ; proteins ; serine |
| Language | English |
| Dates of publication | 2014-0626 |
| Size | p. 2486-2499. |
| Publishing place | Elsevier Ltd |
| Document type | Article |
| ZDB-ID | 80229-3 |
| ISSN | 1089-8638 ; 0022-2836 |
| ISSN (online) | 1089-8638 |
| ISSN | 0022-2836 |
| DOI | 10.1016/j.jmb.2014.04.019 |
| Database | NAL-Catalogue (AGRICOLA) |
More links
Kategorien
In stock of ZB MED Bonn / Germany
| Z 4' 63/108: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.
Inter-library loan at ZB MED
Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.