What question did this study set out to answer?

To determine whether epidermal growth factor receptor (EGFR) lysosomal targeting and down-regulation require intrinsic receptor tyrosine kinase activity or specific sequence motifs.

March 1, 1995Journal of Biological ChemistryOpen Access

Endocytosis and Lysosomal Targeting of Epidermal Growth Factor Receptors Are Mediated by Distinct Sequences Independent of the Tyrosine Kinase Domain

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Authors

LOLee K. Opresko CCChia-Ping Chang BWBirgit H. Will

Discussion

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Overview

In vitro mutagenesis uncovers kinase-independent sorting of epidermal growth factor receptors, indicating distinct sequences direct internalization and degradation.

Key Points

To determine whether epidermal growth factor receptor (EGFR) lysosomal targeting and down-regulation require intrinsic receptor tyrosine kinase activity or specific sequence motifs.
Generated mutant EGFR constructs lacking the conserved tyrosine kinase domain while retaining varying segments of the distal carboxyl-terminal regulatory region.
Measured internalization rates and receptor turnover half-lives (t1/2) in the presence or absence of epidermal growth factor (EGF).
Mutants lacking both the kinase domain and regulatory sequences exhibited slow internalization (0.02 min⁻¹) and prolonged turnover (t1/2 ~24 h), matching unoccupied holo-EGFR.
Kinase-deficient mutants preserving the entire regulatory domain underwent constitutive internalization and lysosomal targeting without EGF, demonstrating turnover rates (t1/2 ~11 h) comparable to occupied wild-type EGFR (t1/2 ~9.5 h).
Enhanced receptor turnover specifically required sequences between residues 945 and 991, demonstrating that internalization and lysosomal targeting are mediated by distinct motifs.

Cite This Study

Opresko et al. (1995) studied this question.

synapsesocial.com/papers/6a1a5086ce473d7c3dc3fcaf https://doi.org/10.1074/jbc.270.9.4325

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March 1, 1995Journal of Biological ChemistryOpen Access

Endocytosis and Lysosomal Targeting of Epidermal Growth Factor Receptors Are Mediated by Distinct Sequences Independent of the Tyrosine Kinase Domain

View Full Paper

Ask AI

Bookmark

Authors

LOLee K. Opresko CCChia-Ping Chang BWBirgit H. Will

Discussion

Member takes

Overview

In vitro mutagenesis uncovers kinase-independent sorting of epidermal growth factor receptors, indicating distinct sequences direct internalization and degradation.

Key Points

To determine whether epidermal growth factor receptor (EGFR) lysosomal targeting and down-regulation require intrinsic receptor tyrosine kinase activity or specific sequence motifs.
Generated mutant EGFR constructs lacking the conserved tyrosine kinase domain while retaining varying segments of the distal carboxyl-terminal regulatory region.
Measured internalization rates and receptor turnover half-lives (t1/2) in the presence or absence of epidermal growth factor (EGF).
Mutants lacking both the kinase domain and regulatory sequences exhibited slow internalization (0.02 min⁻¹) and prolonged turnover (t1/2 ~24 h), matching unoccupied holo-EGFR.
Kinase-deficient mutants preserving the entire regulatory domain underwent constitutive internalization and lysosomal targeting without EGF, demonstrating turnover rates (t1/2 ~11 h) comparable to occupied wild-type EGFR (t1/2 ~9.5 h).
Enhanced receptor turnover specifically required sequences between residues 945 and 991, demonstrating that internalization and lysosomal targeting are mediated by distinct motifs.

Cite This Study

Opresko et al. (1995) studied this question.

synapsesocial.com/papers/6a1a5086ce473d7c3dc3fcaf https://doi.org/10.1074/jbc.270.9.4325

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