Ligand-induced activation of A431 cell epidermal growth factor receptors occurs primarily by an autocrine pathway that acts upon receptors on the surface rather than intracellularly.

摘要: Abstract A431 cells express high numbers of epidermal growth factor (EGF) receptors and produce a ligand for these receptors, transforming factor-alpha (TGF-alpha). We have obtained evidence that the EGF on may be activated through an "autocrine" pathway by investigated whether activation phosphorylation receptor endogenously produced TGF-alpha occurs intracellularly or at cell surface. When were cultured under serum-free conditions, in absence exogenous ligand, found to basal level phosphorylation. labeled culturing with 32Pi continuous presence monoclonal antibodies block binding receptor, decreased 30 +/- 10% level. This reduction could not accounted decrease content attributable down-regulation catabolism resulted from anti-receptor antibodies. The mediated antibody was accompanied accumulation increased levels secreted species culture medium. also pulse-labeled 15 min [35S]cysteine immunoprecipitated lysate anti-phosphotyrosine after various chase periods. Tyrosine-phosphorylated became detectable 40 reached maximum 4-6 h; times are agreement intervals required reach surface synthesis then achieve maximal expression. In addition, only 170-kDa, mature species, 160-kDa intracellular precursor, antibody. results pulse-chase experiments finding can suggest result endogenous (presumably TGF-alpha), which during biosynthesis processing.