The sphingosine 1-phosphate receptor 2 is shed in exosomes from breast cancer cells and is N-terminally processed to a short constitutively active form that promotes extracellular signal regulated kinase activation and DNA synthesis in fibroblasts.

ABSTRACT: We demonstrate here that the G protein-coupled receptor (GPCR), sphingosine 1-phosphate receptor 2 (S1P₂, Mr = 40 kDa) is shed in hsp70⁺ and CD63⁺ containing exosomes from MDA-MB-231 breast cancer cells. The receptor is taken up by fibroblasts, where it is N-terminally processed to a shorter form (Mr = 36 kDa) that appears to be constitutively active and able to stimulate the extracellular signal regulated kinase-1/2 (ERK-1/2) pathway and DNA synthesis. An N-terminally truncated construct of S1P₂, which may correspond to the processed form of the receptor generated in fibroblasts, was found to be constitutively active when over-expressed in HEK293 cells. Analysis based on the available crystal structure of the homologous S1P₁ receptor

SUBMITTER: El Buri A 

PROVIDER: S-EPMC6047680 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature