2026-07-21T07:40:48Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/261292025-12-18T12:55:59Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Martinez, Natalia
author
Garcia-Dominguez, Carlota A
author
Domingo, Beatriz
author
Oliva-Martinez, Jose Luis
author
Zarich-Dimitrievich, Natasha
author
Sanchez, Agustin
author
Gutiérrez-Eisman, Silvia
author
Llopis, Juan
author
Rojas-Cabañeros, Jose Maria
funder
Instituto de Salud Carlos III
funder
Regional Government of Castile-La Mancha (España)
funder
Ministerio de Educación y Ciencia (España)
funder
Asociación Española Contra el Cáncer
funder
Fundación Mutua Madrileña
funder
Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España)
2025-01-24T13:23:05Z
2025-01-24T13:23:05Z
2007-11
Martínez N, García-Domínguez CA, Domingo B, Oliva JL, Zarich N, Sánchez A, Gutiérrez-Eisman S, Llopis J, Rojas JM. Sprouty2 binds Grb2 at two different proline-rich regions, and the mechanism of ERK inhibition is independent of this interaction. Cell Signal. 2007 Nov;19(11):2277-85.
10.1016/j.cellsig.2007.07.008
1873-3913
Cellular signalling
17689925
https://hdl.handle.net/20.500.12105/26129
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.
eng
hSpry2
Grb2
SH3
ERK
FGFR
Sprouty2 binds Grb2 at two different proline-rich regions, and the mechanism of ERK inhibition is independent of this interaction
research article
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