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First published online November 24, 2004
doi: 10.1242/10.1242/jcs.01519

Journal of Cell Science 117, 6007-6017 (2004)
Published by The Company of Biologists 2004
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Research Article

FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity

Xuan Li1, Valerie G. Brunton2, Helen R. Burgar1, Lee M. Wheldon1 and John K. Heath1,*

1 CR-UK Growth Factor Group, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
2 CR-UK Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

* Author for correspondence (e-mail: j.k.heath{at}bham.ac.uk)

Accepted 1 September 2004

Activation of signalling by fibroblast growth factor receptor leads to phosphorylation of the signalling attenuator human Sprouty 2 (hSpry2) on residue Y55. This event requires the presence of the signalling adaptor fibroblast growth factor receptor substrate 2 (FRS2). The phosphorylation of hSpry2 is therefore mediated by an intermediate kinase. Using a SRC family kinase-specific inhibitor and mutant cells, we show that hSpry2 is a direct substrate for SRC family kinases, including SRC itself. Activation of SRC via fibroblast growth factor signalling is dependent upon FRS2 and fibroblast growth factor receptor kinase activity. SRC forms a complex with hSpry2 and this interaction is enhanced by hSpry2 phosphorylation. Phosphorylation of hSpry2 is required for hSpry2 to inhibit activation of the extracellular signal-regulated kinase pathway. These results show that recruitment of SRC to FRS2 leads to activation of signal attenuation pathways.

Key words: FGFR, FRS2, Sprouty, SRC, ERK


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© The Company of Biologists Ltd 2004