Findings on FGF receptor trafficking given editorial comment in Journal of Cell Science
J. Wesche (last author)
New important findings from Haugsten and colleagues at the Department of Biochemistry were recently published in the Journal of Cell Science (impact factor 6,91). The authors investigate the intracellular trafficking of a family of receptor tyrosine kinases that have been implicated in several types of tumours.
(click to enlarge)Many growth factors bind to a host of related receptors. This allows them to have distinct outputs in different circumstances, but how the signalling mechanisms differ is hard to establish - particularly if the receptors are very similar. Fibroblast growth factor receptors (FGFRs) are a case in point. Jørgen Wesche and co-workers have therefore examined whether differences in trafficking of these receptors after they internalize might affect their output. Expressing FGFR1-FGFR4 in HeLa cells that lack endogenous FGFRs, the authors track their movements following FGF treatment by costaining for markers of specific sorting routes. They find that, after internalization, all four receptors enter endosomes. Thereafter the receptors paths diverge: FGFR1-FGFR3 tend to be sorted to lysosomes for degradation (they colocalize with EGF), whereas FGFR4 is recycled (it colocalizes with transferrin). Noting that FGFR4 lacks several lysine residues conserved in FGFR1-FGFR3, Wesche and co-workers speculate that these are potential ubiquitylation sites and indeed show that FGFR4 is less ubiquitylated than its siblings. FGFR4 thus seems to escape ubiquitin-directed destruction. Its recycling could prolong FGF signalling, explaining why it alone promotes progression of some tumors.
From major journals, first or last author from the Institute for Cancer Research
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