J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/02/583/13 $2.00
Volume 136, Number 3, February 10, 1997 583-595

An -Helical Signal in the Cytosolic Domain of the Interleukin 2 Receptor  Chain Mediates Sorting Towards Degradation after Endocytosis

Agathe Subtil, Muriel Delepierre,^* and Alice Dautry-Varsat

Unité de Biologie des Interactions Cellulaires, URA CNRS 1960, and ^* Laboratoire de Résonance Magnétique Nucléaire, URA CNRS 1129, Institut Pasteur, 75724 Paris Cedex 15, France

High-affinity IL2 receptors consist of three components, the , , and  chains that are associated in a noncovalent manner. Both the  and  chains belong to the cytokine receptor superfamily. Interleukin 2 (IL2) binds to high-affinity receptors on the cell surface and IL2-receptor complexes are internalized. After endocytosis, the components of this multimolecular receptor have different intracellular fates: one of the chains, , recycles to the plasma membrane, while the others,  and , are routed towards late endocytic compartments and are degraded. We show here that the cytosolic domain of the  chain contains a 10-amino acid sequence which codes for a sorting signal. When transferred to a normally recycling receptor, this sequence diverts it from recycling. The structure of a 17-amino acid segment of the  chain including this sequence has been studied by nuclear magnetic resonance and circular dichroism spectroscopy, which revealed that the 10 amino acids corresponding to the sorting signal form an amphipathic  helix. This work thus describes a novel, highly structured signal, which is sufficient for sorting towards degradation compartments after endocytosis.

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