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J Biol Chem, Vol. 275, Issue 19, 14124-14131, May 12, 2000

Primary Structure Requirements for Xenopus Nodal-related 3 and a Comparison with Regions Required by Xenopus Nodal-related 2^*

Carin Hansen Ezal, Christopher D. Marion, and William C. Smith

From the Department of Molecular, Cellular, and Developmental Biology, and the Neuroscience Research Institute, University of California, Santa Barbara, California 93106

Transforming growth factor- superfamily members play important roles in the early development of animals. Activin and the Xenopus nodal related proteins 1, 2, and 4 induce muscle actin from Xenopus ectodermal explants, whereas the bone morphogenetic proteins 4 and 7 induce ectoderm to differentiate as epidermis. Bone morphogenetic proteins are antagonized by soluble binding proteins such as noggin and chordin, which leads to expression of neural cell adhesion molecule in animal caps. The transforming growth factor- superfamily member Xenopus nodal-related 3 also induces the neural cell adhesion molecule through inhibition of bone morphogenetic proteins. Therefore, whereas Xenopus nodal-related 2 and 3 share a high amount of sequence homology, they lead to very different cell fates. This study investigates the functional domains that distinguish the activities of these two factors. It was found that mutually exclusive regions of nodal-related 2 and 3 were required for activity. The central region of the mature domain is required for nodal-related 2 to induce muscle actin, whereas the N- and C-terminal ends of the mature domain are required for nodal-related 3 to induce neural cell adhesion molecule. These results help to define the minimal domains required for the unique activities of these factors.

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