Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/21093
Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: Regulator of G-Protein Signalling-14 (RGS14) Regulates the Activation of αMβ2 Integrin during Phagocytosis
Authors: Lim, Jenson
Thompson, Jo
May, Robin C
Hotchin, Neil A
Caron, Emmanuelle
Contact Email: jenson.lim@stir.ac.uk
Issue Date: Jun-2013
Publisher: Public Library of Science
Citation: Lim J, Thompson J, May RC, Hotchin NA & Caron E (2013) Regulator of G-Protein Signalling-14 (RGS14) Regulates the Activation of αMβ2 Integrin during Phagocytosis, PLoS ONE, 8 (6), Art. No.: e69163.
Abstract: Integrin-mediated phagocytosis, an important physiological activity undertaken by professional phagocytes, requires bidirectional signalling to/from αMβ2 integrin and involves Rap1 and Rho GTPases. The action of Rap1 and the cytoskeletal protein talin in activating αMβ2 integrins, in a RIAM-independent manner, has been previously shown to be critical during phagocytosis in mammalian phagocytes. However, the events downstream of Rap1 are not clearly understood. Our data demonstrate that one potential Rap1 effector, Regulator of G-Protein Signalling-14 (RGS14), is involved in activating αMβ2. Exogenous expression of RGS14 in COS-7 cells expressing αMβ2 results in increased binding of C3bi-opsonised sheep red blood cells. Consistent with this, knock-down of RGS14 in J774.A1 macrophages results in decreased association with C3bi-opsonised sheep red blood cells. Regulation of αMβ2 function occurs through the R333 residue of the RGS14 Ras/Rap binding domain (RBD) and the F754 residue of β2, residues previously shown to be involved in binding of H-Ras and talin1 head binding prior to αMβ2 activation, respectively. Surprisingly, overexpression of talin2 or RAPL had no effect on αMβ2 regulation. Our results establish for the first time a role for RGS14 in the mechanism of Rap1/talin1 activation of αMβ2 during phagocytosis.
Type: Journal Article
URI: http://hdl.handle.net/1893/21093
DOI Link: http://dx.doi.org/10.1371/journal.pone.0069163
Rights: © 2013 Lim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Affiliation: Biological and Environmental Sciences
Royal Devon and Exeter NHS Foundation Trust
University of Birmingham
University of Birmingham
Imperial College London

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