title: Association of a 70-kDa tyrosine phosphoprotein with the CD16: zeta: gamma complex expressed in human natural killer cells.
abstract: The CD16: zeta: gamma receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fc gamma domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of zeta and gamma are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the zeta subunit and the phospholipase C gamma-1 and gamma-2 isoforms. Here we show that CD16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16: zeta: gamma receptor complex, results in the tyrosine phosphorylation of a 70 kDa zeta-associated protein (pp70). Similarly, a 70-kDa zeta-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa zeta-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16: zeta: gamma complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA.
authors.forename: E
authors.initials: E
authors.lastname: Vivier
authors.forename: A J
authors.initials: AJ
authors.lastname: da Silva
authors.forename: M
authors.initials: M
authors.lastname: Ackerly
authors.forename: H
authors.initials: H
authors.lastname: Levine
authors.forename: C E
authors.initials: CE
authors.lastname: Rudd
authors.forename: P
authors.initials: P
authors.lastname: Anderson
mesh_terms: D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000032:analysis*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis*; D014443:Tyrosine; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D010750:Phosphoproteins; D017452:Receptors, IgG; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human