Roifman C M, Wang G X, Freedman M, Pan Z Q
Division of Immunology/Allergy, Hospital for Sick Children, Toronto, Ontario, Canada.
J Immunol. 1992 Feb 15;148(4):1136-42.
IL-7 is a glycoprotein involved in the regulation of lymphocyte precursor growth. In addition, it has a comitogenic effect on mature T cells but not on mature B cells. The exact mechanism whereby IL-7R mediates these cell growth properties remains unknown. Because many growth factor receptor systems on various cell types transduce signals by activating a tyrosine kinase, we have studied here the effect of IL-7R ligation on protein tyrosine phosphorylation. We found that human rIL-7 consistently induced tyrosine phosphorylation of five major proteins, of 175, 155, 135, 110, and 85 kDa, and five minor proteins. The effect of human rIL-7 on tyrosine phosphorylation of these substrates was concentration and time dependent. One of the known substrates that is phosphorylated on tyrosine residues after binding of growth factors to their receptors is the phosphoinositide-specific phospholipase C. Several phospholipase C isozymes have been recently recognized; one isozyme, phospholipase C-gamma 1, was demonstrated to be phosphorylated rapidly after ligand binding to the platelet-derived growth factor receptor and the T cell Ag receptor. We show here that, in contrast to Ag receptor ligation, activation of IL-7R does not induce tyrosine phosphorylation on phospholipase C-gamma 1. Consistent with these results, human rIL-7 failed to increase phosphatidylinositol turnover and did not induce a rise in cytosolic free Ca2+ in the thymocytes, mature T cells, or pre-pre-B cells. The results indicate that the IL-7R mediates the activation of the tyrosine phosphorylation pathway but does not induce the phosphatidylinositol-phospholipase C pathway.
白细胞介素 -7 是一种参与淋巴细胞前体生长调节的糖蛋白。此外，它对成熟 T 细胞有协同有丝分裂作用，但对成熟 B 细胞没有。白细胞介素 -7 受体（IL -7R）介导这些细胞生长特性的确切机制仍不清楚。由于多种细胞类型上的许多生长因子受体系统通过激活酪氨酸激酶来转导信号，我们在此研究了 IL -7R 连接对蛋白质酪氨酸磷酸化的影响。我们发现人重组白细胞介素 -7（rIL -7）持续诱导 5 种主要蛋白质（分子量分别为 175、155、135、110 和 85 kDa）以及 5 种次要蛋白质的酪氨酸磷酸化。人 rIL -7 对这些底物酪氨酸磷酸化的影响具有浓度和时间依赖性。生长因子与其受体结合后在酪氨酸残基上磷酸化的已知底物之一是磷酸肌醇特异性磷脂酶 C。最近已识别出几种磷脂酶 C 同工酶；其中一种同工酶磷脂酶 C -γ1，在配体与血小板衍生生长因子受体和 T 细胞抗原受体结合后被证明会迅速磷酸化。我们在此表明，与抗原受体连接相反，IL -7R 的激活不会诱导磷脂酶 C -γ1 上的酪氨酸磷酸化。与这些结果一致，人 rIL -7 未能增加胸腺细胞、成熟 T 细胞或前前 B 细胞中的磷脂酰肌醇周转率，也未诱导胞质游离 Ca²⁺ 升高。结果表明，IL -7R 介导酪氨酸磷酸化途径的激活，但不诱导磷脂酰肌醇 - 磷脂酶 C 途径。
