title: Difference between follistatin isoforms in the inhibition of activin signalling: activin neutralizing activity of follistatin isoforms is dependent on their affinity for activin.
abstract: 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.
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Tokyo 158-8501, Setagaya-ku, Japan. ohashim@vmas.kitasato-u.ac.jp
authors.forename: O
authors.initials: O
authors.lastname: Hashimoto
authors.forename: N
authors.initials: N
authors.lastname: Kawasaki
authors.forename: K
authors.initials: K
authors.lastname: Tsuchida
authors.forename: S
authors.initials: S
authors.lastname: Shimasaki
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: H
authors.initials: H
authors.lastname: Sugino
mesh_terms: D028341:Activins; D015374:Biosensing Techniques; D038681:Follistatin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D020014:K562 Cells; D046911:Macromolecular Substances; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D015533:Transcriptional Activation
chemical_list: D038681:Follistatin; D006023:Glycoproteins; D046911:Macromolecular Substances; D020033:Protein Isoforms; D028341:Activins; D007265:Inhibins