Role of the SHP-2 SH2 domains in the interaction between SHP-2 and CagA. (a) COS-7 cells were cotransfected with expression vectors for HA-tagged CagA and Myc-tagged, WT or mutant SHP-2 lacking one or both of the functional SH2 domains. Cell lysates were subjected to immunoprecipitation (IP) with anti-Myc. Immunoprecipitates and total cell lysates (TCL) were immunoblotted (IB) with the indicated antibodies. N-SH2 domain, C-SH2 domain, and both of the SH2 domains were inactivated in SH2ΔN-Myc, SH2ΔC-Myc, and SH2ΔNC-Myc, respectively. WT: WT 11637-CagA. ABD variant was generated from WT 11637-CagA by replacing the entire EPIYA region with that of F32-CagA. (b) COS-7 cells were cotransfected with expression vectors for HA-tagged CagA and Flag-tagged CagA. Cell lysates were subjected to immunoprecipitation (IP) with anti-Flag. Immunoprecipitates and total cell lysates (TCL) were immunoblotted (IB) with the indicated antibodies. (c) A model of CagA–SHP-2 interaction.