2026-07-21T07:40:47Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/261292025-12-18T12:55:59Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc 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 author 2007-11 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. 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 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