X-RAY CRYSTALLOGRAPHIC STUDIES OF RIBOSOMAL S6 KINASE 2 (RSK2)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 90 kDa核糖体S6激酶2（RSK 2）是一种重要的丝氨酸-苏氨酸激酶，广泛表达于多种生长因子中。RSK通路是癌细胞增殖的关键调节因子。在人类中，RSK 2基因突变表现为Coffin-Lowry综合征，其特征是严重的精神发育迟滞。阐明全长RSK 2的分子结构对于理解其活化机制至关重要。RSK 2属于不常见的丝氨酸-苏氨酸激酶家族，其含有由接头区连接的两个不同的激酶结构域。丝裂原和应激调节激酶1（MSK 1）与RSK 2具有相同的结构域组织。这两种蛋白质RSK 2和MSK 1的晶体结构都不可用。我们计划确定全长RSK 2和MSK 1的晶体结构。我们将需要在Se/Met蛋白的Se边缘能量处进行异常衍射实验，以获得已经纯化的Se/Met全长MSK 1的数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The 90-kDa ribosomal S6 kinase 2 (RSK2) is important serine-threonine kinase broadly expressed in response to various growth factors. RSK pathway is a key regulator of cancer cell proliferation. In humans, RSK2 gene mutations are manifested in Coffin-Lowry syndrome characterized by severe psychomotor retardation. Elucidating the molecular structure of full length RSK2 is essential for understanding its activation mechanism. RSK2 belongs to the family of unusual serine-threonine kinases that contain two distinct kinase domains connected by a linker region. The mitogen- and stress-reguated kinase 1 (MSK1) is close homologue to RSK2 with the same domain organization. The crystal structure of both proteins, RSK2 and MSK1 are not available. We plan to determine crystals structure of full length RSK2 and MSK1. We will need to perform anomalous diffraction experiments at Se-edge energy for Se/Met protein in order to get the data for Se/Met full length MSK1, which is already purified.