Essential role of endocytosis for interleukin-4-receptor-mediated JAK/STAT signalling.
In: Journal of cell science, Jg. 128 (2015-10-15), Heft 20, S. 3781-95
academicJournal
Zugriff:
Many important signalling cascades operate through specialized signalling endosomes, but a corresponding mechanism has as yet not been described for hematopoietic cytokine receptors. Based on live-cell affinity measurements, we recently proposed that ligand-induced interleukin-4 receptor (IL-4R) complex formation and thus JAK/STAT pathway activation requires a local subcellular increase in receptor density. Here, we show that this concentration step is provided by the internalization of IL-4R subunits through a constitutive, Rac1-, Pak- and actin-mediated endocytosis route that causes IL-4R subunits to become enriched by about two orders of magnitude within a population of cortical endosomes. Consistently, ligand-induced receptor dimers are preferentially detected within these endosomes. IL-4 signalling can be blocked by pharmacological inhibitors targeting the actin polymerization machinery driving receptor internalization, placing endocytosis unambigously upstream of receptor activation. Taken together, these observations demonstrate a role for endocytosis that is mechanistically distinct from the scaffolding function of signalling endosomes in other pathways.
(© 2015. Published by The Company of Biologists Ltd.)
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Essential role of endocytosis for interleukin-4-receptor-mediated JAK/STAT signalling.
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Autor/in / Beteiligte Person: | Kurgonaite, K ; Gandhi, H ; Kurth, T ; Pautot, S ; Schwille, P ; Weidemann, T ; Bökel, C |
Zeitschrift: | Journal of cell science, Jg. 128 (2015-10-15), Heft 20, S. 3781-95 |
Veröffentlichung: | Cambridge : Company of Biologists ; <i>Original Publication</i>: London., 2015 |
Medientyp: | academicJournal |
ISSN: | 1477-9137 (electronic) |
DOI: | 10.1242/jcs.170969 |
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