sprouty2 and spred1-2 proteins inhibit the activation of the erk pathway elicited by cyclopentenone prostanoidssprouty2和spred1-2蛋白抑制erk通路的激活环戊烯酮引起的前列腺素类.pdf

Sprouty2 and Spred1-2 Proteins Inhibit the Activation of the ERK Pathway Elicited by Cyclopentenone Prostanoids ´ ´ 1. ´ 1. 1 ´ ´ 1 Carlota A. Garcıa-Domınguez , Natalia Martınez , Teresa Gragera , Andrea Perez-Rodrıguez , Diana 1 ´ 1 ´ ´ 1 ´ 1 ´ 2 ´ 1 Retana , Gonzalo Leon , Agustın Sanchez , Jose Luis Oliva , Dolores Perez-Sala , Jose M. Rojas * ´ ´ ´ ´ 1 Unidad de Biologıa Celular, Area de Biologıa Celular y del Desarrollo, Centro Nacional de Microbiologıa, Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain, ´ ´ ´ ´ 2 Departamento de Biologıa Fısico-Quımica, Centro de Investigaciones Biologicas, C.S.I.C., Ramiro de Maeztu 9, Madrid, Spain Abstract Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor- extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA and 15d-PGJ . Furthermore, we found that in HT cells that do not