2004 Fiscal Year Final Research Report Summary
Intracellular and extracellular control of activin signaling by novel regulatory molecules
| Project/Area Number |
15370058
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SUGINO Hiromu Univ.of Tokushima, Inst.for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (50211305)
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| Co-Investigator(Kenkyū-buntansha) |
TSUCHIDA Kunihiro Univ.of Tokushima, Inst.for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (30281091)
KURISAKI Akira Univ.of Tokushima, Inst.for Enzyme Research, Research Associate, 分子酵素学研究センター, 助手 (60346616)
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| Project Period (FY) |
2003 – 2004
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| Keywords | activin / follistatin / ARIP / FLRG / endocytosis |
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| Research Abstract |
Activins, members of the transforming growth factor (TGF-β) family have various effects on diverse biologic systems, such as erythroid differentiation, bone growth, mesoderm induction, etc.
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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