AN ALPHA-HELICAL SIGNAL IN THE CYTOSOLIC DOMAIN OF THE INTERLEUKIN-2 RECEPTOR-BETA CHAIN MEDIATES SORTING TOWARDS DEGRADATION AFTER ENDOCYTOSIS

High-affinity IL2 receptors consist of three components, the alpha, be ta, and gamma chains that are associated in a noncovalent manner. Both the beta and gamma chains belong to the cytokine receptor superfamily , Interleukin 2 (IL2) binds to high-affinity receptors on the cell sur face and IL2-receptor complexes are internalized. After endocytosis, t he components of this multimolecular receptor have different intracell ular fates: one of the chains, a, recycles to the plasma membrane, whi le the others, beta and gamma, are routed towards late endocytic compa rtments and are degraded, We show here that the cytosolic domain of th e beta chain contains a 10-amino acid sequence which codes for a sorti ng signal. When transferred to a normally recycling receptor, this seq uence diverts it from recycling. The structure of a 17-amino acid segm ent of the beta chain including this sequence has been studied by nucl ear magnetic resonance and circular dichroism spectroscopy, which reve aled that the 10 amino acids corresponding to the sorting signal form an amphipathic alpha helix. This work thus describes a novel, highly s tructured signal, which is sufficient for sorting towards degradation compartments after endocytosis.