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

Signals that can mediate ligand-induced receptor internalization and calcium regulation are present in a 48-amino acid "calcium-internalization" domain in the C' terminus of the epidermal growth factor (EGF) receptor. The basis of calcium and internalization regulation signalled by th...

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Bibliographic Details
Published in:The Journal of biological chemistry 1991-12, Vol.266 (34), p.23467-23470
Main Authors: CHIA-PING CHANG, KAO, J. P. Y, LAZAR, C. S, WALSH, B. J, WELLS, A, STEVEN WILEY, H, GILL, G. N, ROSENFELD, M. G
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
calcium
Calcium - metabolism
Cell Line
Cell receptors
Cell structures and functions
Down-Regulation
Endocytosis
ErbB Receptors - chemistry
ErbB Receptors - metabolism
Fundamental and applied biological sciences. Psychology
Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors
Ligands
Mice
Molecular and cellular biology
Phosphorylation
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Summary:Signals that can mediate ligand-induced receptor internalization and calcium regulation are present in a 48-amino acid "calcium-internalization" domain in the C' terminus of the epidermal growth factor (EGF) receptor. The basis of calcium and internalization regulation signalled by this 48-amino acid sequence was analyzed using deletion and substitution mutant receptors. Cells expressing truncated receptors containing either the NH2- or COOH-terminal portion of the 48-residue domain displayed high affinity EGF-dependent endocytosis and receptor down-regulation. These endocytosis-competent EGF receptor mutants that lacked any autophosphorylation site were unable to increase the concentration of intracellular calcium. To investigate the role of self-phosphorylation in EGF-induced calcium mobilization, phenylalanine was substituted for the single autophosphorylated tyrosine residue in this region of an internalization-competent truncated receptor. The receptor-mediated calcium response was abolished, while ligand-dependent receptor internalization was unimpaired. These results demonstrate that EGF-dependent receptor endocytosis and calcium mobilization are separate events. Tyrosine self-phosphorylation is required for increased [Ca2+]i, while structural features distinct from autophosphorylation are required for receptor internalization.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)54520-8