No Jak, No Receptor

Science's STKE  02 Apr 2002:
Vol. 2002, Issue 126, pp. tw125
DOI: 10.1126/stke.2002.126.tw125

The oncostatin M receptor (OSMR) is a cytokine receptor that associates with members of the Janus family of tyrosine kinases (Jaks). Jak-1, in particular, is critical for signaling by the OSMR because it phosphorylates residues on the receptor that then associate with other key signaling proteins. Radgke et al. now present evidence that Jak1 also is critical for expression of the OSMR at the cell surface. Transfected OSMR was more abundant at the cell surface when Jak1 was also expressed. Studies with mutant OSMR or Jak-1 proteins showed that the effect appeared to require the direct interaction of the receptor with the kinase but did not require activity of Jak-1. In human fibrosarcoma cell lines that don't express Jak1, expression of the OSMR at the cell surface was reduced, but could e restored by expression of the kinase. The OSMR appears to have a membrane-proximal region that inhibits expression at the cell surface. If this portion of the receptor was removed, Jak-1 was no longer required for efficient expression of the receptor at the cell surface. The authors propose that the observed properties of the OSMR provide a quality-control mechanism by which only receptors with properly associated Jak-1 are transported to the plasma membrane.

S. Radtke, H. M. Hermanns, C. Haan, H. Schmitz-Van de Leur, H. Gascan, P. C. Heinrich, I. Behrmann, Novel role of Janus kinase 1 in the regulation of oncostatin M receptor surface expression. J. Biol. Chem. 277: 11297-11305 (2002). [Abstract] [Full Text]