Identification of a basolateral sorting signal within the cytoplasmic domain of the interleukin-6 signal transducer gp130.
Interleukin-6-type cytokine receptors are expressed in polarized cells such as hepatocytes and intestinal cells. For the interleukin-6-receptor gp80 and its signal transducer gp130, a preferential basolateral localization was demonstrated in Madin-Darby canine kidney (MDCK) cells and two basolateral sorting signals were identified within the cytoplasmic domain of gp80. The cytoplasmic tail of gp130 is responsible for signaling via the Janus kinase/signal transducer and activator of transcription pathway. In addition, it mediates the internalization of the receptor complex which is dependent on a di-leucine motif. Truncated gp130 lacking the cytoplasmic domain is sorted apically in MDCK cells. For identification of the basolateral sorting signal(s) of gp130, a series of deletion mutants in the cytoplasmic domain of gp130 have been generated and stably expressed in MDCK cells. Biotinylation analyses of these mutants show that a ten amino acids sequence between amino acids 782 and 792 which contains the di-leucine internalization motif is also essential for a basolateral sorting. Accordingly, we detect apical delivery of a gp130 mutant in which the di-leucine motif has been exchanged by two alanines (gp130LL/AA). These findings indicate that the di-leucine motif which directs the internalization of the IL-6 receptor complex also mediates the basolateral sorting of the signal transducer gp130.
Doumanov
Jordan A
JA
Institut für Biologische Chemie und Ernährungswissenschaft, Universität Hohenheim, Garbenstr. 30, D-70599 Stuttgart, Germany.
Daubrawa
Merle
M
Unden
Heike
H
Graeve
Lutz
L
D020816:Amino Acid Motifs; D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000737:chemistry* / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D021382:Protein Sorting Signals / Q000502:physiology*; D017434:Protein Structure, Tertiary
D015850:Interleukin-6; D021382:Protein Sorting Signals; D050822:Cytokine Receptor gp130; D007930:Leucine