Clevenger C V, Medaglia M V
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia 19104.
Mol Endocrinol. 1994 Jun;8(6):674-81. doi: 10.1210/mend.8.6.7935483.
The clonal expansion of antigen-stimulated T-lymphocytes during an immune response is mediated by several lymphokines. Strong evidence now exists that the neuroendocrine hormone PRL is necessary, but not sufficient, for T-cell proliferation. Little is known, however, of the signal transduction mechanisms of the PRL receptor (PRLR) within T-cells. We demonstrate here that PRL stimulation of the T-cell line Nb2 induced the concentration- and time-dependent activation of the protein tyrosine kinase p59fyn, but not of four other src family protein tyrosine kinases. Activation of fyn was also observed in Concanavalin-A-primed peripheral blood lymphocytes stimulated with PRL and in Nb2 cells incubated with anti-PRLR antibodies. The activation of fyn by PRL stimulation correlated with Nb2 cell proliferation. Immunoblot analysis of anti-fyn and anti-PRLR immune complexes revealed an association between each PRLR isoform and p59fyn. These studies demonstrate for the first time an association between the PRLR and a src family protein tyrosine kinase affiliated with signal transduction.
免疫应答过程中抗原刺激的T淋巴细胞的克隆性扩增是由多种淋巴因子介导的。现在有强有力的证据表明，神经内分泌激素催乳素（PRL）对于T细胞增殖是必要的，但并不充分。然而，关于T细胞内PRL受体（PRLR）的信号转导机制却知之甚少。我们在此证明，PRL对T细胞系Nb2的刺激可诱导蛋白酪氨酸激酶p59fyn浓度和时间依赖性的激活，但不会诱导其他四种src家族蛋白酪氨酸激酶的激活。在用PRL刺激的伴刀豆球蛋白A预处理的外周血淋巴细胞以及用抗PRLR抗体孵育的Nb2细胞中也观察到了fyn的激活。PRL刺激引起的fyn激活与Nb2细胞增殖相关。抗fyn和抗PRLR免疫复合物的免疫印迹分析显示，每种PRLR异构体与p59fyn之间存在关联。这些研究首次证明了PRLR与参与信号转导的src家族蛋白酪氨酸激酶之间存在关联。
