Essential role of endocytosis for interleukin-4-receptor-mediated JAK/STAT signalling
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Pages (from-to) | 3781-95 |
Number of pages | 15 |
Journal | Journal of cell science |
Volume | 128 |
Issue number | 20 |
Publication status | Published - 15 Oct 2015 |
Peer-reviewed | Yes |
External IDs
Scopus | 84946033967 |
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ORCID | /0000-0001-5624-1717/work/142239019 |
Keywords
Keywords
- Endocytosis/physiology, HEK293 Cells, Humans, Interleukin-4 Receptor alpha Subunit/genetics, Janus Kinases/genetics, STAT Transcription Factors/genetics, Signal Transduction/physiology