We investigated whether aggregation of the low-affinity immunoglobulin G receptor (CD16) on human NK cells results in receptor ubiquitination. We found that the CD16 ζ subunit becomes ubiquitinated in response to receptor engagement. We then investigated whether protein tyrosine kinase (PTK) activation is required for CD16-mediated receptor ubiquitination. Pretreatment with the PTK inhibitor genistein substantially decreased ligand-induced ζ ubiquitination, suggesting a requirement for PTK activation in receptor ubiquitination. We further analyzed PTK involvement in controlling receptor ubiquitination by using the vaccinia virus expression system. Overexpression of wild-type active lck, but not a kinase-deficient mutant, enhanced both ligand-induced tyrosine phosphorylation and ubiquitination of the CD16 ζ subunit. Taken together, our data demonstrate that CD16 engagement induces ζ chain ubiquitination and strongly suggest a role for lck in regulating this modification.
|Number of pages||9|
|Journal||European Journal of Immunology|
|Publication status||Published - 1999|
- Fc receptor
- NK cell
- Signal transduction
ASJC Scopus subject areas