Binding, internalization, and intracellular processing of proteins interacting with recycling receptors. A kinetic analysis

Z. Bajzer, A. C. Myers, S. Vuk-Pavlovic

Research output: Contribution to journalArticle

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Abstract

We measured time-dependent concentration changes of human interferon-α2a (IFN) and human tumor necrosis factor-α (TNF) bound at the plasma membrane and internalized by human lung alveolar carcinoma A549 cells in the presence of excess free ligand. Concentration changes for these two ligands were substantially different. We modified our compartmental kinetic model encompassing receptor synthesis and receptor loss (Myers, A.C., Kovach, J.S., and Vuk-Pavlovic, S. (1987) J. Biol. Chem. 262, 6494-6499) to include receptor recycling. We solved analytically the equations of three variants of the model of receptor recycling. All parameters (rate constants) were identifiable when the data sets consisted of time-resolved concentrations of IFN and TNF at the cell surface and internalized by cells. By least squares fitting we derived the best fit values for the first order rate constants for internalization of the ligand-receptor complex, receptor recycling, turnover of free receptors, elimination of the ligand from cells, and the rate of insertion of free receptors into the membrane. The best fit to data for interactions of cells with IFN was obtained without inclusion of the term for recycling of receptors to the membrane. The simplest model including receptor recycling was necessary and sufficient for the fit to the respective data for TNF. These results demonstrate that the contribution of receptor recycling to the metabolism of the ligand and the receptor can be quantitated by compartmental modeling. Receptor recycling does not contribute to the kinetics of Type I IFN receptor in A549 cells. In contrast, recycling contributes significantly to endocytosis mediated by the TNF receptor.

Original languageEnglish (US)
Pages (from-to)13623-13631
Number of pages9
JournalJournal of Biological Chemistry
Volume264
Issue number23
StatePublished - 1989

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Recycling
Ligands
Kinetics
Interferons
Processing
Proteins
Tumor Necrosis Factor-alpha
Interferon alpha-beta Receptor
Bronchiolo-Alveolar Adenocarcinoma
Membranes
Tumor Necrosis Factor Receptors
Rate constants
Endocytosis
Least-Squares Analysis
Cell Communication
Interferon Type I
Cell Membrane
Cell membranes
Lung
Metabolism

ASJC Scopus subject areas

  • Biochemistry

Cite this

Binding, internalization, and intracellular processing of proteins interacting with recycling receptors. A kinetic analysis. / Bajzer, Z.; Myers, A. C.; Vuk-Pavlovic, S.

In: Journal of Biological Chemistry, Vol. 264, No. 23, 1989, p. 13623-13631.

Research output: Contribution to journalArticle

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