The isoforms of phospholipase C-gamma are differentially used by distinct human NK activating receptors.
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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Related Subject Headings
- Tyrosine
- Type C Phospholipases
- T-Lymphocytes, Cytotoxic
- Recombinant Fusion Proteins
- Receptors, Natural Killer Cell
- Receptors, Immunologic
- Receptors, Fc
- Phosphorylation
- Phospholipase C gamma
- NK Cell Lectin-Like Receptor Subfamily K
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tyrosine
- Type C Phospholipases
- T-Lymphocytes, Cytotoxic
- Recombinant Fusion Proteins
- Receptors, Natural Killer Cell
- Receptors, Immunologic
- Receptors, Fc
- Phosphorylation
- Phospholipase C gamma
- NK Cell Lectin-Like Receptor Subfamily K