Tyrosine phosphorylation of BIT on photic stimulation in the rat retina
Tyrosine phosphorylation of BIT on photic stimulation in the rat retina
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DOI：
10.1016/s0014-5793(03)01493-5
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发表时间：
2004-01-16
期刊：
影响因子：
3.5
通讯作者：
Nagai, K
中科院分区：
文献类型：
--
作者：
Hamada, J;Okumura, N;Nagai, K
BIT是一种跨膜糖蛋白，在其胞外区具有三个免疫球蛋白样结构域，在其胞质区具有酪氨酸磷酸化位点。我们以前已经表明，BIT是酪氨酸磷酸化的下丘脑视交叉上核在黑暗期间的光暴露的反应，并建议它参与了光夹带的昼夜节律钟。为了进一步研究BIT在神经系统中的功能，我们检测了光刺激对大鼠视网膜中BIT酪氨酸磷酸化的影响。结果发现，视网膜中BIT的酪氨酸磷酸化水平在光照期高于黑暗期。此外，在黑暗期间的光刺激导致BIT的快速磷酸化和随后的BIT与SHP-2的关联。当光关闭时，磷酸化状态迅速恢复。光依赖性磷酸化的BIT也观察到在离体培养的视网膜，这是由一个特定的Src家族抑制剂，PP-2。免疫组化结果显示，BIT在视网膜的内、外丛状层中高度富集，并与抗SHP-2抗体呈免疫反应性。这些结果表明，BIT的酪氨酸磷酸化参与视网膜神经元的传递。(C)2003年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
BIT is a transmembrane glycoprotein with three immunoglobulin-like domains in its extracellular region and tyrosine phosphorylation sites in its cytosolic region. We have previously shown that BIT was tyrosine phosphorylated in the hypothalamic suprachiasmatic nucleus in response to light exposure during the dark period, and suggested that it was involved in the light entrainment of the circadian clock. To further investigate the function of BIT in the nervous system, we examined the effect of photic stimulation on its tyrosine phosphorylation in the rat retina. It was found that the tyrosine phosphorylation level of BIT in the retina was higher in the light period than in the dark period. In addition, a light stimulation during the dark period resulted in a rapid phosphorylation of BIT and a subsequent association of BIT with SHP-2. The phosphorylation state was quickly reverted when the light was turned off. The light-dependent phosphorylation of BIT was also observed in isolated cultured retinas, and this was blocked by a specific Src-family inhibitor, PP-2. Immunohistochemical study showed that BIT was highly enriched in the inner and outer plexiform layers in the retina, where the immunoreactivity to anti-SHP-2 antibody was also detected. These results suggest that tyrosine phosphorylation of BIT is involved in neuronal transmission in the retina. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.