TY - JOUR
T1 - Difference between follistatin isoforms in the inhibition of activin signalling
T2 - Activin neutralizing activity of follistatin isoforms is dependent on their affinity for activin
AU - Hashimoto, Osamu
AU - Kawasaki, Nana
AU - Tsuchida, Kunihiro
AU - Shimasaki, Shunichi
AU - Hayakawa, Takao
AU - Sugino, Hiromu
N1 - Funding Information:
We thank Dr. Y. Eto for supplying the recombinant human activin A and Dr. J. Massagué for providing the p3TP-Lux construct. We are also grateful to Drs. N. Hoshi and Y. Hasegawa of Kitasato University for useful discussion and reading the manuscript. This work was supported in part by grants-in-aid from the Ministry of Health and Welfare of Japan.
PY - 2000/8
Y1 - 2000/8
N2 - 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.
AB - 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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U2 - 10.1016/S0898-6568(00)00099-1
DO - 10.1016/S0898-6568(00)00099-1
M3 - Article
C2 - 11027950
AN - SCOPUS:0034253201
SN - 0898-6568
VL - 12
SP - 565
EP - 571
JO - Cellular Signalling
JF - Cellular Signalling
IS - 8
ER -