TY - JOUR
T1 - Novel factors in regulation of activin signaling
AU - Tsuchida, Kunihiro
AU - Nakatani, Masashi
AU - Matsuzaki, Takashi
AU - Yamakawa, Norio
AU - Liu, Zhonghui
AU - Bao, Yongli
AU - Arai, Koji Y.
AU - Murakami, Tatsuya
AU - Takehara, Yuka
AU - Kurisaki, Akira
AU - Sugino, Hiromu
N1 - Funding Information:
We thank Drs. Y. Hasegawa, O. Hashimoto, and K. Inokuchi for helpful discussions. We also thank Dr. M. Koike for the FLRG antibody. This research was supported by the Ministry of Education, Science, Sports and Culture of Japan and by grants from The Yamanouchi Foundation for Research on Metabolic disorders, The Fujisawa foundation, and Kyowa Hakko Kogyo Co. Ltd. to K. Tsuchida.
PY - 2004/10/15
Y1 - 2004/10/15
N2 - Activin type II receptors (ActRIIs) are the primary receptors that transmit the activin signal to intracellular signaling pathways. Binding of activins to ActRIIs recruits the activin type I receptor and initiates downstream signaling. We have found that PDZ proteins, named activin receptor-interacting proteins (ARIPs), specifically associate with ActRIIs. We have studied the mechanism that ARIPs regulate cell surface expression and cellular localization of ActRIIs. ARIP2 interacts with both ActRIIs and RalBP1 (Ral binding protein 1) through different domains to dramatically change the localization of ActRIIs. Overexpression of ARIP2 enhances endocytosis of ActRIIs. These data indicate that ARIP2 is a novel factor regulating cell surface ActRII expression and activin function. A novel activin binding protein, follistatin-related gene (FLRG) was identified. FLRG protein binds activin and myostatin with a high affinity. The biological activity of FLRG is similar to those of follistatin, however, the regulation and expression patterns of follistatin and FLRG differ. Immunohistochemical analysis shows that FLRG is distributed in spermatogenic cells of the testis, renal tubules, epithelial cells of the lung, and myocardium. Thus, although structurally and functionally similar, follistatin and FLRG likely play distinct roles as activin/GDF binding proteins in vivo.
AB - Activin type II receptors (ActRIIs) are the primary receptors that transmit the activin signal to intracellular signaling pathways. Binding of activins to ActRIIs recruits the activin type I receptor and initiates downstream signaling. We have found that PDZ proteins, named activin receptor-interacting proteins (ARIPs), specifically associate with ActRIIs. We have studied the mechanism that ARIPs regulate cell surface expression and cellular localization of ActRIIs. ARIP2 interacts with both ActRIIs and RalBP1 (Ral binding protein 1) through different domains to dramatically change the localization of ActRIIs. Overexpression of ARIP2 enhances endocytosis of ActRIIs. These data indicate that ARIP2 is a novel factor regulating cell surface ActRII expression and activin function. A novel activin binding protein, follistatin-related gene (FLRG) was identified. FLRG protein binds activin and myostatin with a high affinity. The biological activity of FLRG is similar to those of follistatin, however, the regulation and expression patterns of follistatin and FLRG differ. Immunohistochemical analysis shows that FLRG is distributed in spermatogenic cells of the testis, renal tubules, epithelial cells of the lung, and myocardium. Thus, although structurally and functionally similar, follistatin and FLRG likely play distinct roles as activin/GDF binding proteins in vivo.
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U2 - 10.1016/j.mce.2004.02.006
DO - 10.1016/j.mce.2004.02.006
M3 - Conference article
C2 - 15451561
AN - SCOPUS:4644256757
SN - 0303-7207
VL - 225
SP - 1
EP - 8
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
T2 - Proceedings of the International Workshop on Inhibins,
Y2 - 3 July 2003 through 4 July 2003
ER -