Schaeffer E M, Debnath J, Yap G, McVicar D, Liao X C, Littman D R, Sher A, Varmus H E, Lenardo M J, Schwartzberg P L
National Human Genome Research Institute, National Cancer Institute, National Institute for Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Science. 1999 Apr 23;284(5414):638-41. doi: 10.1126/science.284.5414.638.
T cell receptor (TCR) signaling requires activation of Zap-70 and Src family tyrosine kinases, but requirements for other tyrosine kinases are less clear. Combined deletion in mice of two Tec kinases, Rlk and Itk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitro and adaptive immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in rlk-/-itk-/- cells, but intermediate events including inositol trisphosphate production, calcium mobilization, and mitogen-activated protein kinase activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-gamma activation.
T细胞受体（TCR）信号传导需要Zap-70和Src家族酪氨酸激酶的激活，但对其他酪氨酸激酶的需求尚不清楚。小鼠中两种Tec激酶Rlk和Itk的联合缺失导致TCR反应出现明显缺陷，包括体外增殖、细胞因子产生和凋亡，以及体内对刚地弓形虫的适应性免疫反应。TCR下游的分子事件在rlk-/-itk-/-细胞中是完整的，但包括三磷酸肌醇产生、钙动员和丝裂原活化蛋白激酶激活在内的中间事件受损，确立了Tec激酶是磷脂酶C-γ激活所需的TCR信号传导的关键调节因子。
