Ligand-induced internalization and increased cell calcium are mediated via distinct structural elements in the carboxyl terminus of the epidermal growth factor receptor.

摘要: Abstract Signals that can mediate ligand-induced receptor internalization and calcium regulation are present in a 48-amino acid "calcium-internalization" domain the C' terminus of epidermal growth factor (EGF) receptor. The basis signalled by this sequence was analyzed using deletion substitution mutant receptors. Cells expressing truncated receptors containing either NH2- or COOH-terminal portion 48-residue displayed high affinity EGF-dependent endocytosis down-regulation. These endocytosis-competent EGF mutants lacked any autophosphorylation site were unable to increase concentration intracellular calcium. To investigate role self-phosphorylation EGF-induced mobilization, phenylalanine substituted for single autophosphorylated tyrosine residue region an internalization-competent receptor-mediated response abolished, while ligand-dependent unimpaired. results demonstrate mobilization separate events. Tyrosine is required increased [Ca2+]i, structural features distinct from internalization.