TY - JOUR
T1 - Interaction between lck and syk family tyrosine kinases in Fcγ receptor- initiated activation of natural killer cells
AU - Ting, A. T.
AU - Dick, C. J.
AU - Schoon, R. A.
AU - Karnitz, L. M.
AU - Abraham, R. T.
AU - Leibson, P. J.
PY - 1995
Y1 - 1995
N2 - Ligation of the FcγR on natural killer (NK) cells results in the tyrosine phosphorylation of multiple substrates critical for intracellular signaling and activation of NK cell effector functions. However, it remains unclear which nonreceptor protein-tyrosine kinases (PTK) participate in this process. In this report we demonstrate that FcγR ligation induced the tyrosine phosphorylation and increased the catalytic activities of both syk family PTKs, ZAP-70, and syk. The phosphorylation of ZAP-70 and syk was enhanced markedly by overexpression of wild-type lck but not by a kinase-inactive mutant, suggesting that early FcγR-initiated activation of lck results in the subsequent regulation of syk family PTKs. The regulatory interplay between src and syk family PTKs was emphasized further by the observation that lck overexpression enhanced the association of ZAP-70 with the ζ chain of the FcγR complex. Additional analyses indicated that lck induced the subsequent tyrosine phosphorylation of phospholipase C (PLC)-γ2. Interestingly, the regulatory effects of lck on ZAP-70, syk, and PLC-γ2 could not be replaced by overexpression of either fyn or src, demonstrating a selective role for lck in effectively coupling FcγR stimulation to critical downstream signaling events. Taken together, our results suggest not only that FcγR stimulation on NK cells is coupled to the intracellular activation of both ZAP-70 and syk, but that the src family member, lck, can selectively regulate this tyrosine kinase cascade.
AB - Ligation of the FcγR on natural killer (NK) cells results in the tyrosine phosphorylation of multiple substrates critical for intracellular signaling and activation of NK cell effector functions. However, it remains unclear which nonreceptor protein-tyrosine kinases (PTK) participate in this process. In this report we demonstrate that FcγR ligation induced the tyrosine phosphorylation and increased the catalytic activities of both syk family PTKs, ZAP-70, and syk. The phosphorylation of ZAP-70 and syk was enhanced markedly by overexpression of wild-type lck but not by a kinase-inactive mutant, suggesting that early FcγR-initiated activation of lck results in the subsequent regulation of syk family PTKs. The regulatory interplay between src and syk family PTKs was emphasized further by the observation that lck overexpression enhanced the association of ZAP-70 with the ζ chain of the FcγR complex. Additional analyses indicated that lck induced the subsequent tyrosine phosphorylation of phospholipase C (PLC)-γ2. Interestingly, the regulatory effects of lck on ZAP-70, syk, and PLC-γ2 could not be replaced by overexpression of either fyn or src, demonstrating a selective role for lck in effectively coupling FcγR stimulation to critical downstream signaling events. Taken together, our results suggest not only that FcγR stimulation on NK cells is coupled to the intracellular activation of both ZAP-70 and syk, but that the src family member, lck, can selectively regulate this tyrosine kinase cascade.
UR - http://www.scopus.com/inward/record.url?scp=0029057410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029057410&partnerID=8YFLogxK
U2 - 10.1074/jbc.270.27.16415
DO - 10.1074/jbc.270.27.16415
M3 - Article
C2 - 7541798
AN - SCOPUS:0029057410
SN - 0021-9258
VL - 270
SP - 16415
EP - 16421
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 27
ER -