IDENTIFICATION OF A REGION WITHIN THE CYTOPLASMIC DOMAIN OF THE INTERLEUKIN-6 (IL-6) SIGNAL TRANSDUCER GP130 IMPORTANT FOR LIGAND-INDUCED ENDOCYTOSIS OF THE IL-6 RECEPTOR

Interleukin-6 (IL-6) exerts its action via a cell surface receptor com plex consisting of two subunits, the IL-6 receptor and the signal tran sducer gp130. We have studied the role of both transmembrane proteins for IL-6 internalization and ligand-induced down-regulation of cell su rface receptors. Co-expression of wild-type and mutant forms of both t he IL-6 receptor and gp130 in transiently transfected COS-7 cells reve aled that gp130 is essential for efficient endocytosis and receptor do wn-regulation. Whereas the cytoplasmic domain of the IL-6 receptor is not significantly involved in the internalization process, deletion of the corresponding domain of gp130 resulted in an almost complete loss of the ability to endocytose IL-6. Mutants with different truncations within the intracellular domain of gp130 revealed that a 10-amino aci d sequence TQPLLDSEER is crucial for efficient internalization. Since this sequence contains a putative di-leucine internalization motif, we suggest that a di-leucine motif directs the receptor mediated endocyt osis of the IL-6 receptor complex.