SELECTIVE BINDING OF SHC-SH2 DOMAIN TO TYROSINE-PHOSPHORYLATED ZETA-CHAIN BUT NOT GAMMA-CHAIN UPON CD16 LIGATION ON HUMAN NK CELLS

FC gamma RIII (CD16) is a hetero-oligomeric receptor composed of a lig and-binding alpha subunit associated with home- or heterodimers of the TCR zeta- and Fc epsilon RI gamma-chains. We have previously demonstr ated that CD16 ligation promotes complex formation between tyrosine-ph osphorylated she and Grb2, leading to activation of ras signaling path way in human NK cells. Here we report that CD16 engagement induces rap id she association with the tyrosine-phosphorylated receptor complex i n human NK cells. In vitro binding studies demonstrate that this inter action is mediated by the shc-SH2 domain, and immunodepletion experime nts indicate that the zeta- but not the gamma-chain has the capability to mediate this association. Jurkat cell clones expressing CD16-zeta or -gamma homodimers have been used to gain more information about the mechanism of shc/CD16 association. Our data show that, while engageme nt of both receptors induces tyrosine phosphorylation of she and Grb2 recruitment, shc-SH2/receptor complex association is evident only in C D16-zeta but not in CD16-gamma transfectants. Overall, our data demons trate that the adaptor protein she can be recruited to the activated C D16 complex by interaction with tyrosine-phosphorylated zeta-chain in a SH2-dependent manner. These results also provide further support to the notion that zeta- and gamma-chains might couple to different bioch emical pathways.