Department of Biotechnology, Indian Institute of Technology Kharagpur, India.
Advanced Technology Development Centre, Indian Institute of Technology Kharagpur, India.
FEBS Lett. 2020 Jan;594(2):266-277. doi: 10.1002/1873-3468.13590. Epub 2019 Sep 11.
This study aimed to identify the intracellular binding partner of a unique class of staphylococcal secreted exotoxins called superantigen-like proteins (SSL) from human macrophage and keratinocyte cell lysates. Here, we report that SSL1 specifically binds to human extracellular signal-regulated kinase 2 (hERK2), an important stress-activated kinase in mitogen-activated protein kinase signaling pathways. Western blot and in vitro binding studies with recombinant hERK2 confirmed the binding interaction of SSL1, SSL7, and SSL10 with hERK2. Moreover, the SSLs-hERK2 interaction was validated biochemically by ELISA. Our finding shows that SSLs play a novel role by binding with host cell MAP kinase signaling pathway protein. Understanding the SSL-hERK2 interaction will also provide a basis for designing SSL-based peptide inhibitors of hERK2 in cancer therapy.
本研究旨在鉴定一种独特的葡萄球菌分泌外毒素（称为超抗原样蛋白，SSL）的细胞内结合伴侣，该毒素来自人巨噬细胞和角质形成细胞的裂解物。在这里，我们报告 SSL1 特异性结合人细胞外信号调节激酶 2（hERK2），它是丝裂原激活蛋白激酶信号通路中一种重要的应激激活激酶。用重组 hERK2 进行 Western blot 和体外结合研究证实了 SSL1、SSL7 和 SSL10 与 hERK2 的结合相互作用。此外，ELISA 还验证了 SSLs-hERK2 相互作用的生物化学性质。我们的发现表明 SSL 通过与宿主细胞 MAP 激酶信号通路蛋白结合发挥新的作用。了解 SSL-hERK2 相互作用也将为设计基于 SSL 的 hERK2 肽抑制剂在癌症治疗中的应用提供基础。
