Jeon Hye-Kyung, Ahn Jeong-Hun, Choe Jongseon, Park Jeon Han, Lee Tae H
Department of Biology, Yonsei University, Shinchon-dong 134, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Immunol Lett. 2005 May 15;98(2):303-10. doi: 10.1016/j.imlet.2004.12.005. Epub 2005 Jan 5.
Heterogeneous nuclear ribonucleoprotein K protein (hnRNP K) has diverse molecular partners implicated in signal transduction pathways, and is tyrosine-phosphorylated in response to growth factors and oxidative stress. Among the structurally distinct domains of hnRNP K, an SH3-binding domain (SH3BD) has been known to promote the association of SH3-containing tyrosine kinases and protooncoprotein Vav, which are involved in B cell receptor (BCR) signalling. In this study, we analyzed proteins of Ramos B cell line that are altered upon BCR activation with anti-IgM antibody, revealing that a certain hnRNP K isoform is up-regulated in response to anti-IgM treatment. We also showed that hnRNP K is tyrosine-phosphorylated after BCR ligation. HnRNP K lacking the SH3BD is shown not to interact with phosphorylated Vav, and Ramos cells stably expressing this mutant protein are less susceptible to anti-IgM-induced apoptosis, indicating that hnRNP K is coupled to BCR-mediated signalling and its SH3BD is required for proper signal propagation. Our results provide the first evidence that hnRNP K is involved in BCR signalling pathway.
异质性细胞核核糖核蛋白K（hnRNP K）有多种参与信号转导途径的分子伴侣，并且在生长因子和氧化应激反应中发生酪氨酸磷酸化。在hnRNP K结构不同的结构域中，已知一个SH3结合结构域（SH3BD）可促进含SH3的酪氨酸激酶和原癌蛋白Vav的结合，它们参与B细胞受体（BCR）信号传导。在本研究中，我们分析了用抗IgM抗体激活BCR后发生改变的Ramos B细胞系的蛋白质，发现某种hnRNP K异构体在抗IgM处理后上调。我们还表明，BCR连接后hnRNP K发生酪氨酸磷酸化。缺失SH3BD的hnRNP K不与磷酸化的Vav相互作用，稳定表达这种突变蛋白的Ramos细胞对抗IgM诱导的凋亡敏感性较低，表明hnRNP K与BCR介导的信号传导相关联，其SH3BD是正确信号传导所必需的。我们的结果首次证明hnRNP K参与BCR信号通路。
