This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by McPherson, V. A.
Right arrow Articles by Craig, A. W. B.
PubMed
Right arrow PubMed Citation
Right arrow Articles by McPherson, V. A.
Right arrow Articles by Craig, A. W. B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2009, p. 389-401, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.00904-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Contributions of F-BAR and SH2 Domains of Fes Protein Tyrosine Kinase for Coupling to the Fc{varepsilon}RI Pathway in Mast Cells{triangledown} ,{dagger}

Victor A. McPherson,1,{ddagger} Stephanie Everingham,1,{ddagger} Robert Karisch,1 Julie A. Smith,1 Christian M. Udell,1 Jimin Zheng,1 Zongchao Jia,1 and Andrew W. B. Craig1,2*

Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada,1 Queen's University Cancer Research Institute, Division of Cancer Biology and Genetics, Kingston, Ontario K7L 3N6, Canada2

Received 6 June 2008/ Returned for modification 18 July 2008/ Accepted 29 October 2008

This study investigates the roles of Fer-CIP4 homology (FCH)-Bin/amphiphysin/Rvs (F-BAR) and SH2 domains of Fes protein tyrosine kinase in regulating its activation and signaling downstream of the high-affinity immunoglobulin G (IgE) receptor (Fc{varepsilon}RI) in mast cells. Homology modeling of the Fes F-BAR domain revealed conservation of some basic residues implicated in phosphoinositide binding (R113/K114). The Fes F-BAR can bind phosphoinositides and induce tubulation of liposomes in vitro. Mutation of R113/K114 to uncharged residues (RK/QQ) caused a significant reduction in phosphoinositide binding in vitro and a more diffuse cytoplasmic localization in transfected COS-7 cells. RBL-2H3 mast cells expressing full-length Fes carrying the RK/QQ mutation show defects in Fc{varepsilon}RI-induced Fes tyrosine phosphorylation and degranulation compared to cells expressing wild-type Fes. This correlated with reduced localization to Lyn kinase-containing membrane fractions for the RK/QQ mutant compared to wild-type Fes in mast cells. The Fes SH2 domain also contributes to Fes signaling in mast cells, via interactions with the phosphorylated Fc{varepsilon}RI β chain and the actin regulatory protein HS1. We show that Fes phosphorylates C-terminal tyrosine residues in HS1 implicated in actin stabilization. Thus, coordinated actions of the F-BAR and SH2 domains of Fes allow for coupling to Fc{varepsilon}RI signaling and potential regulation the actin reorganization in mast cells.

* Corresponding author. Mailing address: Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada. Phone: (613) 533-2496. Fax: (613) 533-6830. E-mail: ac15{at}queensu.ca

{triangledown} Published ahead of print on 10 November 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} V.A.M. and S.E. contributed equally to this work.

Molecular and Cellular Biology, January 2009, p. 389-401, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.00904-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»