Journal
JOURNAL OF IMMUNOLOGY
Volume 175, Issue 1, Pages 213-218Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.1.213
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- NCI NIH HHS [CA47752] Funding Source: Medline
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The two isoforms of phospholipase C (PLC)-gamma couple immune recognition receptors to important calcium- and protein kinase C-dependent cellular functions. It has been assumed that PLC-gamma 1 and PLC-gamma 2 have redundant functions and that the receptors can use whichever PLC-gamma 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-gamma 1 or PLC-gamma 2, whereas the novel NK cell-activating receptor NKG2D preferentially couples to PLC-gamma 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-gamma 1 and PLC-gamma 2 both regulate the functions of ITAM-containing receptors, whereas only PLC-gamma 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-gamma. More broadly, these observations reveal a basis for selectively targeting the functions initiated by distinct immune recognition receptors.
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