The isoforms of phospholipase C-γ are differentially used by distinct human NK activating receptors

Jadee L. Upshaw, Renee A. Schoon, Christopher J. Dick, Daniel D. Billadeau, Paul J. Leibson

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


The two isoforms of phospholipase C (PLC)-γ couple immune recognition receptors to important calcium- and protein kinase C-dependent cellular functions. It has been assumed that PLC-γ1 and PLC-γ2 have redundant functions and that the receptors can use whichever PLC-γ 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-γ1 or PLC-γ2, whereas the novel NK cell-activating receptor NKG2D preferentially couples to PLC-γ2. 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-γ1 and PLC-γ2 both regulate the functions of ITAM-containing receptors, whereas only PLC-y2 regulates the function of DAP10-coupled receptors. These data suggest that specific immune recognition receptors can differentially couple to the two isoforms of PLC-γ. More broadly, these observations reveal a basis for selectively targeting the functions initiated by distinct immune recognition receptors.

Original languageEnglish (US)
Pages (from-to)213-218
Number of pages6
JournalJournal of Immunology
Issue number1
StatePublished - Jul 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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