We demonstrate the difference between the follistatin isoforms (FS-288 and FS-315), two activin-binding proteins, in the neutralizing activity for activin signalling. Transcriptional reporter assay using 3TP-Lux, an activin- responsive reporter construct, showed that the inhibitory effect of FS-288 on activin-induced transcriptional response is more potent than that of FS-315. The potency was not influenced by the presence of heparan sulfates, by which FS, in particular FS-288, associates with cell surfaces at a high affinity. Furthermore, FS-288 inhibited the binding of activin to its type II receptor more markedly than did FS-315, as evidenced by surface plasmon resonance and affinity cross-linking experiments. Moreover, the Kd of FS-288 and FS-315 for activin A was estimated to be 46.5 ± 0.37 pM and 432 ± 26 pM, respectively, by surface plasmon resonance experiments. These results indicate that the different potency between the two FS isoforms in the inhibition of activin activities depends on their affinity for activin A. (C) 2000 Elsevier Science Inc.
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