TY - JOUR
T1 - CD69-triggered ERK activation and functions are negatively regulated by CD94/NKG2-A inhibitory receptor
AU - Zingoni, Alessandra
AU - Palmieri, Gabriella
AU - Morrone, Stefania
AU - Carretero, Marta
AU - Lopez-Botel, Miguel
AU - Piccoli, Mario
AU - Frati, Luigi
AU - Santoni, Angela
PY - 2000
Y1 - 2000
N2 - CD69 represents a functional triggering molecule on activated NK and T cells, capable of inducing cytotoxic activity and costimulating cytokine production. It belongs to the C-lectin type superfamily, and its gene maps in the NK gene complex, close to other genes coding for NK receptors. CD94/NKG2-A complex is the inhibitory receptor for the non classical MHC class I molecule HLA-E on human NK cells. To investigate CD69-initiated signal transduction pathways, and to evaluate CD94/NKG2-A interference on CD69 triggering ability, we have generated transfectants expressing both receptors in the RBL eel line. Here we report that CD69 engagement leads to the activation of extracellular signal-regulated kinase (ERK) enzymes belonging to the MAPK family, and that this event is required for CD69-mediated cell degranulation. Moreover, we show that the co-engagement of CD94/NKG2-A inhibitory receptor effectively suppresses both CD69-triggered cell degranulation in RBL transfectants, through the inhibition of ERK activation, and CD69-induced cytotoxicity in human NK cells. Thus, here we provide new information on the molecular mechanisms initiated by CD69 activation receptor, and show that CD69-initiated signaling pathways and functional activity are negatively regulated by CD94/NKG2-A inhibitory complex.
AB - CD69 represents a functional triggering molecule on activated NK and T cells, capable of inducing cytotoxic activity and costimulating cytokine production. It belongs to the C-lectin type superfamily, and its gene maps in the NK gene complex, close to other genes coding for NK receptors. CD94/NKG2-A complex is the inhibitory receptor for the non classical MHC class I molecule HLA-E on human NK cells. To investigate CD69-initiated signal transduction pathways, and to evaluate CD94/NKG2-A interference on CD69 triggering ability, we have generated transfectants expressing both receptors in the RBL eel line. Here we report that CD69 engagement leads to the activation of extracellular signal-regulated kinase (ERK) enzymes belonging to the MAPK family, and that this event is required for CD69-mediated cell degranulation. Moreover, we show that the co-engagement of CD94/NKG2-A inhibitory receptor effectively suppresses both CD69-triggered cell degranulation in RBL transfectants, through the inhibition of ERK activation, and CD69-induced cytotoxicity in human NK cells. Thus, here we provide new information on the molecular mechanisms initiated by CD69 activation receptor, and show that CD69-initiated signaling pathways and functional activity are negatively regulated by CD94/NKG2-A inhibitory complex.
KW - CD69
KW - Inhibitory receptor
KW - NK cell
KW - Signal transduction
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U2 - 10.1002/1521-4141(200002)30:2<644::AID-IMMU644>3.0.CO;2-H
DO - 10.1002/1521-4141(200002)30:2<644::AID-IMMU644>3.0.CO;2-H
M3 - Article
C2 - 10671222
AN - SCOPUS:0033970117
VL - 30
SP - 644
EP - 651
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 2
ER -