Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Meenhuis, A; Irandoust, M; Wölfler, A; Roovers, O; Valkhof, M; Touw, IP.
Janus kinases promote cell-surface expression and provoke autonomous signalling from routing-defective G-CSF receptors.
Biochem J. 2009; 417(3):737-746
Doi: 10.1042/BJ20081153
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- Co-Autor*innen der Med Uni Graz
- Wölfler Albert
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- Abstract:
- CSF3R [G-CSF (granulocyte colony-stimulating factor) receptor] controls survival, proliferation and differentiation of myeloid progenitor cells via activation of multiple JAKs (Janus kinases). In addition to their role in phosphorylation of receptor tyrosine residues and downstream signalling substrates, JAKs have recently been implicated in controlling expression of cytokine receptors, predominantly by masking critical motifs involved in endocytosis and lysosomal targeting. In the present study, we show that increasing the levels of JAK1, JAK2 and TYK2 (tyrosine kinase 2) elevated steady-state CSF3R cell-surface expression and enhanced CSF3R protein stability in haematopoietic cells. This effect was not due to inhibition of endocytotic routing, since JAKs did not functionally interfere with the dileucine-based internalization motif or lysine-mediated lysosomal degradation of CSF3R. Rather, JAKs appeared to act on CSF3R in the biosynthetic pathway at the level of the ER (endoplasmic reticulum). Strikingly, increased JAK levels synergized with internalization- or lysosomal-routing-defective CSF3R mutants to confer growth-factor independent STAT3 (signal transducer and activator of transcription 3) activation and cell survival, providing a model for how increased JAK expression and disturbed intracellular routing of CSF3R synergize in the transformation of haematopoietic cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Line, Tumor -
- Cell Membrane - metabolism
- Endocytosis -
- Hela Cells -
- Humans -
- Janus Kinases - metabolism
- Ligands -
- Lysosomes - metabolism
- Mice -
- Receptors, Colony-Stimulating Factor - genetics
- Receptors, Granulocyte Colony-Stimulating Factor - genetics
- Signal Transduction -
- Transfection -
- Ubiquitination -
- Find related publications in this database (Keywords)
- endocytosis
- granulocyte colony-stimulating factor (G-CSF) receptor
- Janus kinase (JAK)
- signal transducer and activator of transcription 3 (STAT3)
- signal transduction