Figure 6.

Schematic of the pathway by which LPA increases LPP3 expression. Our data suggest that LPA activates the PI3K–AKT pathway through LPA receptors (LPA1/3) to increase PI3K–AKT activity, which then activates NF-κB through the canonical pathway involving dissociation and ubiquitin-dependent degradation of inhibitory IκB protein, resulting in nuclear translocation of RelA/P50 or RelB/P52 transcriptional activator complexes. These activated NF-κB complexes then bind to the Rel response elements in the PLPP3 promoter that were identified in this study to initiate PLPP3 gene transcription. GPCR, G protein–coupled receptors.