Table 2.
CD226 axis receptor ICD mutational studies and associated functional effects.
| Receptor | System (cell type) | Modifications | Finding(s) | Ref. |
|---|---|---|---|---|
| CD226 (human) | BW5147 (T cell line, mouse), human CD226 ectopic | S329F mutation; various truncations of intracellular domain | Prevention of protein kinase C (PKC) phosphorylation and subsequent cellular adhesion | (31) |
| CD226 (human) | Jurkat and NKL (T and NK cell lines, human) | WT in NKL cells. Mutation of S329F in Jurkat cells | S329F mutant failed to associate with LFA-1 | (32) |
| CD226 (human) | Jurkat (T cell line, human) and COS-7 (fibroblast line, monkey) | Y322F | Fyn induced phosphorylation at Y322, abrogated by Y322F mutation. | (32) |
| CD226 (mouse) | Primary murine NK cells and YTS (human NK cell line) | Ectopic expression of mouse CD226 in YTS cells | Increased phosphorylation of Erk and Akt, as well as calcium flux and target cell lysis following CD226 engagement | (30) |
| CD226 (mouse) | YTS (NK cell line, human) and transgenic mice | Y319F, S326A | Y319F modification in CD226 attenuated mouse NK cell cytotoxicity and IFNg production | (30) |
| CD226 (mouse) | Synthetic peptide corresponding to 315-333 of mouse CD226 | Synthesized with phosphorylation at Y319, D321Q | Phosphorylation of the amino acid corresponding to Y319 led to capture of Grb2. Mutation of the asparagine at +2 position led to loss of Grb2 binding | (30) |
| CD226 (human) | Jurkat (T cell line, human) or primary (T cells, human) | Y322A, S329A | Y322A modification, but not S329A, reduced downstream CD226 signaling after incubation with CHO-OKT3-PVR cells | (33) |
| TIGIT (human) | Jurkat (T cell line, human) | Y225A, Y231A | Y225A/Y231A dual mutation rescued CD69 expression on Jurkat cells following exposure to superantigen and CD155 | (33) |
| TIGIT (human) | YTS (NK cell line, human) | Truncation (Y231stop); Y231A | Rescue of CD155-TIGIT induced inhibition of YTS (NK) mediated cytotoxicity following truncation or Y231A mutation in TIGIT | (10) |
| TIGIT (human) | YTS (NK cell line, human) | Y225A, Y231A | CD155 induced TIGIT phosphorylation. Pervanadate treatment-induced phosphorylation of TIGIT was prevented with Y225A or Y225A/Y231A, but not Y231A alone | (34) |
| TIGIT (human) | YTS (NK cell line, human) | Y225A, Y231A | TIGIT Y225 associates with Grb2, leading to downstream inhibitory function. Nominal rescue of cytotoxicity with Y231A mutation | (34) |
| TIGIT (human) | YTS (NK cell line, human) | Y225A, Y231A | Reduced association with β-arrestin 2 following mutation Y225A or Y225A/Y231A, but not Y231A alone | (35) |
| TIGIT (human) | Jurkat (T cell line, human) | ICD truncation, Y225F, Y231F | TIGIT intracellular domain is not required to prevent PVR-induced CD226 phosphorylation | (36) |
| TIGIT (human) | Cell-free liposome | ICD expressed on cell-free liposome | Lack of Shp2, Shp1, Zap70, Grb2, SHIP-1, or P50a recruitment following phosphorylation of TIGIT ICD by Fyn | (36) |
| CD96 | Undescribed | Undescribed | Undescribed | None |
| PVRIG (human) | HEK293T (kidney cell line, human) and MOLT4 (T cell line, human) | Y233F, Y293F | Y233F mutation reduced phosphorylation after pervanadate treatment. PVRIG associates with SHIP and Shp1/2 following pervanadate treatment | (9) |