Ras activation in response to lysophosphatidic acid requires a permissive input from the epidermal growth factor receptor.
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 G(i/o)-proteins and requires a permissive input from basal EGFR activity.
Rubio
Ignacio
I
Institute of Molecular Cell Biology, Medical Faculty, Friedrich-Schiller-University, Drackendorfer Strasse 1, 07747 Jena, Germany. b5igru@rz.uni-jena.de
Rennert
Knut
K
Wittig
Ute
U
Wetzker
Reinhard
R
D000818:Animals; D019556:COS Cells; D066246:ErbB Receptors / Q000378:metabolism* / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D006150:Guanine Nucleotides / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*
D006150:Guanine Nucleotides; D008246:Lysophospholipids; D037342:Pertussis Toxin; D066246:ErbB Receptors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D016283:Proto-Oncogene Proteins p21(ras)