Epidermal growth factor induces lysophosphatidic acid type 1 receptor regulation through phosphorylation

Abstract

Lysophosphatidic acid (LPA) is a local hormone/autacoid/ growth factor involved in many cellular responses such as: cell migration, proliferation and surviving, platelet aggregation, smooth muscle contraction, neurotransmitter release, establishment of focal adhesions, neurite retraction and cell rounding (among many others). The actions of LPA are mediated through a family of G protein coupled receptors (GPCRs) that includes five subtypes LPA1‐5 receptors which can couple to different G proteins. Phosphorylation of GPCRs is one of the earliest events that regulate their function. Current evidence indicates that homologous desensitization of these receptors mainly involves G protein‐coupled receptor kinases (GRKs), whereas in heterologous desensitization second messenger‐activated kinases play a key role. The primary goal of this work was to study the possibly regulation of LPA1 receptor induced by EGF receptor activation. The LPA1 receptor, tagged with the green fluorescent protein, was transfected into C9 cells. Stimulation with LPA induces an increase in intracellular calcium concentration, LPA1 receptor phosphorylation and internalization. Activation of EGF receptors decreases (50%) LPA‐induced intracellular calcium increase. In addition, EGF receptor activation also induced LPA1 receptor phosphorylation and internalization. This "crosstalk" seems to involve protein kinase C, since pharmacological inhibitors markedly decreased EGF‐induced LPA1 receptor phosphorylation.This research was partially supported by Grants from DGAPA (IN206302) and CONACyT (079908).