Acta Biochim Biophys Sin 2005,37(3): Critical Role of Cys168 in Noggin Protein's Biological Function

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ISSN 1672-9145 Acta Biochim Biophys Sin 2005, 37(3): 181–185 CN 31-1940/Q

Critical Role of Cys168 in Noggin Protein’s Biological Function

Wei-Dong LIU, Xiang-Ling FENG, Cai-Ping REN, Jian-Ling SHI, Xu-Yu YANG, Ming ZHAO, Liang ZHOU, Ke LAN, and Kai-Tai YAO*

Cancer Research Institute, Central South University, Changsha 410078, China

Abstract Previous studies have indicated that noggin exerts its neural inducing effect by binding and antagonizing bone morphogenetic protein 4 (BMP4). In order to further clarify the relationship between the structure and the function of noggin, and elucidate the possible mechanism responsible for noggin-BMP4 interaction, we generated three noggin mutants, C168S, C174S and C197S, by using a site-directed mutagenesis method. Ectopic expression of wild-type (WT) noggin, C174S or C197S, in Xenopus animal caps (ACs) by mRNA injection converted the explants (prospective ectoderm) into neural tissue, as indicated by the neural-like morphology and expression of the neural cell adhesion molecule (NCAM) in the ACs. In contrast, ACs expressing C168S suffered an epidermal fate similar to the control caps. Similarly, among the three mutants, only C168S lost the dorsalizing function. These studies highlight the critical role played by Cys168 in noggin’s biological activities. It probably participates in the formation of an intermolecular disulfide bridge.

Key words noggin; site-directed mutagenesis; neural induction; dorsalizing

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Received: November 8, 2004 Accepted: January 17, 2005

This work was supported by a grant from Joint Research Scheme Project of National Natural Science Foundation of China and the Hong Kong Research Grants Council (No. 39910161994)

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