Ras activation in response to lysophosphatidic acid requires a permissive input from the epidermal growth factor receptor

Author:

RUBIO Ignacio1,RENNERT Knut1,WITTIG Ute1,WETZKER Reinhard1

Affiliation:

1. Institute of Molecular Cell Biology, Medical Faculty, Friedrich-Schiller-University, Drackendorfer Strasse 1, 07747 Jena, Germany

Abstract

The topology of the signalling pathway linking the G-protein-coupled receptor agonist lysophosphatidic acid (LPA) to extracellular-signal-regulated kinase activation remains undeciphered. In the present study, we report that analysis of LPA signals at the level of Ras-GTP formation and Ras nucleotide exchange discriminates true mediatory signals from permissive activities that do not participate in signal relay. Hence, whereas pertussis toxin (PTX) treatment impairs stimulation of nucleotide exchange, epidermal growth factor receptor (EGFR) inhibition does not compromise LPA-induced acceleration of nucleotide exchange, but instead attenuates basal nucleotide turnover on Ras. Our data indicate that LPA activation of Ras proceeds via PTX-sensitive Gi/o-proteins and requires a permissive input from basal EGFR activity.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

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