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Are Differentially Used by Distinct Human NK Activating Receptors 1
* Department of Immunology, and Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905
The two isoforms of phospholipase C (PLC)-
couple immune recognition receptors to important calcium- and protein kinase C-dependent cellular functions. It has been assumed that PLC-1 and PLC-2 have redundant functions and that the receptors can use whichever PLC- isoform is preferentially expressed in a cell of a given hemopoietic lineage. In this study, we demonstrate that ITAM-containing immune recognition receptors can use either PLC-1 or PLC-2, whereas the novel NK cell-activating receptor NKG2D preferentially couples to PLC-2. Experimental models evaluating signals from either endogenous receptors (FcR vs NKG2D-DAP10) or ectopically expressed chimeric receptors (with ITAM-containing cytoplasmic tails vs DAP10-containing cytoplasmic tails) demonstrate that PLC-1 and PLC-2 both regulate the functions of ITAM-containing receptors, whereas only PLC-2 regulates the function of DAP10-coupled receptors. These data suggest that specific immune recognition receptors can differentially couple to the two isoforms of PLC-. More broadly, these observations reveal a basis for selectively targeting the functions initiated by distinct immune recognition receptors.
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