Novel factors in regulation of activin signaling

Kunihiro Tsuchida, Masashi Nakatani, Takashi Matsuzaki, Norio Yamakawa, Zhonghui Liu, Yongli Bao, Koji Y. Arai, Tatsuya Murakami, Yuka Takehara, Akira Kurisaki, Hiromu Sugino

Research output: Contribution to journalConference article

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume225
Issue number1-2
DOIs
Publication statusPublished - 15-10-2004
EventProceedings of the International Workshop on Inhibins, - Siena, Italy
Duration: 03-07-200304-07-2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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    Tsuchida, K., Nakatani, M., Matsuzaki, T., Yamakawa, N., Liu, Z., Bao, Y., Arai, K. Y., Murakami, T., Takehara, Y., Kurisaki, A., & Sugino, H. (2004). Novel factors in regulation of activin signaling. Molecular and Cellular Endocrinology, 225(1-2), 1-8. https://doi.org/10.1016/j.mce.2004.02.006