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Ligand for the NKG2D receptor, together with at least ULBP1 and ULBP3. ULBPs activate multiple signalingpathways in primary NK cells, resulting in the production of cytokines and chemokines. Binding of ULBPs ligands toNKG2D induces calcium mobilization and activation of the JAK2, STAT5, ERK and PI3K kinase/Akt signal transductionpathway. In CMV infected cells, interacts with soluble CMV glycoprotein UL16. The interaction with UL16 blocked theinteraction with the NKG2D receptor, providing a mechanism by which CMV infected cells might escape the immune system.UL16 also causes ULBP2 to be retained in the ER and cis-Golgi apparatus so that it does not reach the cell surface