Tyrosine kinase-dependent ubiquitination of CD16 zeta subunit in human NK cells following receptor engagement.
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 zeta 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 zeta 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 zeta subunit. Taken together, our data demonstrate that CD16 engagement induces zeta chain ubiquitination and strongly suggest a role for lck in regulating this modification.
Paolini
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R
Department of Experimental Medicine and Pathology, Institute Pasteur-Fondazione Cenci Bolognetti, University "La Sapienza", Rome, Italy. fmainiero@axrma.uniroma1.it
Serra
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A
Molfetta
R
R
Piccoli
M
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Frati
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L
Santoni
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D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
D015703:Antigens, CD; D010446:Peptide Fragments; D017452:Receptors, IgG; D014452:Ubiquitins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)