Cell adhesion regulates ubiquitin-mediated degradation of the platelet-derived growth factor receptor beta

Cross-talk between integrin-mediated adhesion and growth factors has been d escribed in many recent studies; however, the underlying mechanisms remain incompletely understood. We report here that detachment of cells from the e xtracellular matrix induced a decrease in both the autophosphorylation and protein levels of the platelet-derived growth factor receptor beta (PDGF-R beta), which was completely reversed upon replating cells on fibronectin. T he effect occurred in all cells examined but to a greater extent in primary fibroblasts compared with established cell lines. Decreased PDGF-R levels in suspended cells correlated with ubiquitination of the PDGF-R and was blo cked by treatment with inhibitors of the proteasome pathway. Unlike PDGF-in duced down-regulation, detachment-induced degradation did not require recep tor autophosphorylation, internalization, or tyrosine kinase activity. me c onclude that cell detachment results in cellular desensitization to PDGF th at is mediated by degradation of the PDGF-R via a novel ubiquitin-dependent pathway.