Document Detail

Sprouty2 binds Grb2 at two different proline-rich regions, and the mechanism of ERK inhibition is independent of this interaction.
MedLine Citation:
PMID:  17689925     Owner:  NLM     Status:  MEDLINE    
Sprouty2 has been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. Sprouty2 directly interacts with the adapter protein Grb2, member of the receptor tyrosine kinase-induced signaling pathways. In considering the functional role of Grb2, we investigated whether the interaction with this protein was responsible for ERK pathway inhibition. We found that the binding between Sprouty2 and Grb2 is constitutive, independent of Sprouty2 tyrosine phosphorylation, although it is increased when fibroblast growth factor receptor is activated. This connection is mediated by the N-terminal SH3 domain of Grb2 and two Sprouty2 proline-rich stretches (residues 59-64 and 303-307). Most importantly, a double Sprouty2 mutant (hSpry2 P59AP304A), which is unable to bind Grb2, developed at a similar inhibition level of fibroblast growth factor receptor-ERK pathway than that which originated from Sprouty2 wt. These results are evidence that the Sprouty2 mechanism of ERK inhibition is independent of Grb2 binding.
Natalia Martínez; Carlota A García-Domínguez; Beatriz Domingo; José Luis Oliva; Natasha Zarich; Agustín Sánchez; Silvia Gutiérrez-Eisman; Juan Llopis; José M Rojas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-14
Journal Detail:
Title:  Cellular signalling     Volume:  19     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-09-10     Completed Date:  2007-11-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  2277-85     Citation Subset:  IM    
Unidad de Biología Celular, Centro Nacional de Microbiología, Instituto de Salud Carlos III, carretera Majadahonda-Pozuelo, Km 2, Majadahonda-28220, Madrid, Spain.
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MeSH Terms
Amino Acid Sequence
Binding Sites
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
Fluorescence Resonance Energy Transfer
GRB2 Adaptor Protein / chemistry,  metabolism*
Intracellular Signaling Peptides and Proteins / chemistry,  metabolism*
Molecular Sequence Data
Mutation / genetics
NIH 3T3 Cells
Proline / metabolism*
Protein Binding
Protein Interaction Mapping
Protein Transport
Signal Transduction
ras Proteins / metabolism
src Homology Domains
Reg. No./Substance:
0/GRB2 Adaptor Protein; 0/Intracellular Signaling Peptides and Proteins; 0/SPRY2 protein, human; 147-85-3/Proline; EC Signal-Regulated MAP Kinases; EC Proteins

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