Grb141s a Negative Regulator of CEACAM3-mediated Phagocytosis of Pathogenic Bacteria

Background: CEACAM3-mediated phagocytosis is an innate mechanism to eliminate CEACAM-binding pathogenic bacteria. Results: Biochemical analyses and FRET-FUM imaging reveal the direct binding of the adaptor protein Grb14 to the tyrosine-phosphorylated cytoplasmic domain of CEACAM3, and this in~eraction limits phagocytosis. Conclusion: Grb14 is a negative regulator ofCEACAM3-mediated phagocytosis. Significance: Deciphering CEACAM3 interaction partners illuminates the minimal set of cellular factors controlling phagocytosis. Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) is a phagocytic receptor on human granulocytes, which mediates the opsonin-independent recognition and internalization of a restricted set of Gram-negative bacteria such as Neisseria gonorrhoeae. In an unbiased screen using a SH2 domain micro array we identified the SH2 domain of growth factor receptor-bound protein 14 (Grb14) as a novel binding partner of CEACAM3. Biochemical assays and micro