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Updated: Aug 9, 2026

qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes
Published on: March 6, 2019
The isoforms of phospholipase C-gamma are differentially used by distinct human NK activating receptors
Jadee L Upshaw1, Renee A Schoon, Christopher J Dick
1Department of Immunology, and Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Abstract:
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-gamma1 and PLC-gamma2 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-gamma1 or PLC-gamma2, whereas the novel NK cell-activating receptor NKG2D preferentially couples to PLC-gamma2. 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-gamma1 and PLC-gamma2 both regulate the functions of ITAM-containing receptors, whereas only PLC-gamma2 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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