Schieven G L, Kirihara J M, Gilliland L K, Uckun F M, Ledbetter J A
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Mol Biol Cell. 1993 May;4(5):523-30. doi: 10.1091/mbc.4.5.523.
UV radiation is known to induce lymphocyte nonresponsiveness both in vitro and in vivo. We have found that UV radiation rapidly induced tyrosine phosphorylation and calcium signaling in normal human peripheral blood lymphocytes. In the leukemic T cell line Jurkat and the Burkitt's lymphoma cell line Ramos, UV rapidly induced tyrosine phosphorylation in a wavelength-dependent manner, giving strong signals after UVB and UVC, but not UVA, irradiation. Similarly, in Jurkat cells UV-induced calcium signals were dependent on the dose of UVB or UVC irradiation over a range of 150-1200 J/m2, but only a small signal was observed for UVA at a dose of 1200 J/m2. The UV-induced calcium signals were blocked by the tyrosine kinase inhibitor herbimycin A, indicating that they were dependent on tyrosine phosphorylation. Phospholipase C (PLC) gamma 1 was tyrosine phosphorylated in response to UV irradiation but to a lesser extent than observed after CD3 cross-linking. However, PLC gamma 1-associated proteins demonstrated to bind to the PLC gamma 1 SH2 domain were tyrosine phosphorylated strongly after UV irradiation. A similar dose response was observed for the inhibition by herbimycin A of UV-induced calcium signals and UV-induced tyrosine phosphorylation of PLC gamma 1 and associated proteins. We propose that in contrast to CD3/Ti stimulation, UV aberrantly triggers lymphocyte signal transduction pathways by a mechanism that bypasses normal receptor control.
已知紫外线辐射在体外和体内均可诱导淋巴细胞无反应性。我们发现，紫外线辐射能迅速诱导正常人外周血淋巴细胞中的酪氨酸磷酸化和钙信号传导。在白血病T细胞系Jurkat和伯基特淋巴瘤细胞系Ramos中，紫外线以波长依赖的方式迅速诱导酪氨酸磷酸化，在UVB和UVC照射后产生强烈信号，但UVA照射后则无此现象。同样，在Jurkat细胞中，紫外线诱导的钙信号在150 - 1200 J/m²范围内依赖于UVB或UVC照射剂量，但在1200 J/m²的UVA剂量下仅观察到微弱信号。紫外线诱导的钙信号被酪氨酸激酶抑制剂赫曲霉素A阻断，表明它们依赖于酪氨酸磷酸化。磷脂酶C（PLC）γ1在紫外线照射后发生酪氨酸磷酸化，但其程度低于CD3交联后观察到的程度。然而，与PLCγ1 SH2结构域结合的PLCγ1相关蛋白在紫外线照射后酪氨酸磷酸化强烈。对于赫曲霉素A对紫外线诱导的钙信号以及PLCγ1和相关蛋白的紫外线诱导酪氨酸磷酸化的抑制作用，观察到了类似的剂量反应。我们提出，与CD3/Ti刺激相反，紫外线通过一种绕过正常受体控制的机制异常触发淋巴细胞信号转导途径。
