This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01837-07v1 28/10/3372    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Lonic, A. Articles by Guthridge, M. A. PubMed PubMed Citation Articles by Lonic, A. Articles by Guthridge, M. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2008, p. 3372-3385, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.01837-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Fibroblast Growth Factor Receptor 2 Phosphorylation on Serine 779 Couples to 14-3-3 and Regulates Cell Survival and Proliferation

Cell Growth and Differentiation Laboratory, Division of Human Immunology, Hanson Institute, Institute of Medical and Veterinary Science,¹ Department of Medicine, University of Adelaide, Adelaide,² School of Molecular and Microbial Sciences and Institute for Molecular Bioscience, Brisbane, Queensland, Australia³

Received 10 October 2007/ Returned for modification 26 November 2007/ Accepted 15 February 2008

The fibroblast growth factors (FGFs) exert their diverse (or pleiotropic) biological responses through the binding and activation of specific cell surface receptors (FGFRs). While FGFRs are known to initiate intracellular signaling through receptor tyrosine phosphorylation, the precise mechanisms by which the FGFRs regulate pleiotropic biological responses remain unclear. We now identify a new mechanism by which FGFR2 is able to regulate intracellular signaling and cellular responses. We show that FGFR2 is phosphorylated on serine 779 (S779) in response to FGF2. S779, which lies adjacent to the phospholipase C binding site at Y766, provides a docking site for the 14-3-3 phosphoserine-binding proteins and is essential for the full activation of the phosphatidylinositol 3-kinase and Ras/mitogen-activated protein kinase pathways. Furthermore, S779 signaling is essential for promoting cell survival and proliferation in both Ba/F3 cells and BALB/c 3T3 fibroblasts. This new mode of FGFR2 phosphoserine signaling via the 14-3-3 proteins may provide an increased repertoire of signaling outputs to allow the regulation of pleiotropic biological responses. In this regard, we have identified conserved putative phosphotyrosine/phosphoserine motifs in the cytoplasmic domains of diverse cell surface receptors, suggesting that they may perform important functional roles beyond the FGFRs.

Published ahead of print on 10 March 2008.