WKYMVm-induced cross-talk between FPR2 and HGF receptor in human prostate epithelial cell line PNT1A

Cross-communication between GPCRs and TKRs represents a mechanism to amplify the information exchange throughout the cell. We show that WKYMVm, an FPR2 agonist, induces the phosphorylation of Y1313/Y1349/Y1356 residues of c-Met and triggers some of the molecular responses elicited by c-Met/HGF binding, such as STAT3, PLC-gamma 1/PKC alpha and PI3K/Akt pathways. The critical role of NADPH oxidase-dependent superoxide generation in this cross-talk mechanism is supported by the finding that blockade of NADPH oxidase function prevents c-Met trans-phosphorylation and the downstream signalling cascade. These results highlight the function of FPR2 to activate a interconnected signalling network and suggest novel possibilities for therapeutic interventions. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.