Molecular Cloning of the Mouse Activin βESubunit Gene

doi:10.1006/bbrc.1996.1715

Biochemical and Biophysical Research Communications

Volume 228, Issue 3, 21 November 1996, Pages 669-674

https://doi.org/10.1006/bbrc.1996.1715 Get rights and content

Abstract

cDNA clones encoding a novel activin β subunit have been isolated from mouse liver cDNA library. An amino acid homology comparison among members of the TGF-β superfamily indicates that the open reading frame codes for a new activin/inhibin β subunit. The predicted mature region of the subunit shows >60% identity with activin β_Cand β_Dand ≥45% identity with activin β_Aand β_B, but only 20-40% amino acid sequence identity with other TGF-β superfamily members. Therefore, the novel subunit has been designated activin β_E. Alignment of the mature growth factor region of the five activin β subunits revealed that activin β_Aand β_Bshare 63% amino acid identity, while activin β_C, β_D, and β_Eshare 62% identity. Therefore, activin β_Aand β_Bare most related to one another, while activin β_C, β_D, and β_Emay represent a subset of related sequences.

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Cited by (130)

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2021, General and Comparative Endocrinology
Inhibin and Activin, belong to the transforming growth factor β superfamily (TGF-β), which associate with the regulation of the reproductive process by the modulation of the hypothalamic-pituitary-gonad (HPG) axis. In this study, we reported the molecular cloning and tissue expression of inhibin α in allotriploid crucian carp and its parent- diploid red crucian carp. The full-length cDNA of inhibin α were respectively 1632 bp and 1642 bp in allotriploids and diploids, which both consisted of a 1044 bp open reading frame (ORF) encoding 347 amino acids. Real-time quantitative PCR (RT-qPCR) showed that allotriploids and diploids had significant expression of inhibin α in testis and ovary, and the expression of inhibin α in the gonads of allotriploids was higher than that of diploids. The immunohistochemistry indicated that the ovarian development of allotriploids was abnormal, and the expression of Inhibin α in the ovary of allotriploids was higher than that of diploids. Results of co-immunoprecitation (co-IP) demonstrated that the Inhibin α and Activin β_A, Inhibin α and Activin β_B can form dimers. These findings suggested that the elevated expression of inhibin α and the competitive binding of Inhibin α subunit with Activin β subunits in allotriploids may be releted to the sterility of allotriploids. Furthermore, these results will facilitate the investigation of reproduction characteristics in allotriploids and provide theoretical basis for the study of polyploid breeding in the future.
Activin
2021, Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research
Activins are dimeric proteins composed of β_A- and β_A-subunits (activin A), β_B- and β_B-subunits (activin B), or β_A- and β_B-subunits (activin AB). Mature β_A- and β_B-subunits have nine cysteine residues that are required for inter- and intramolecular disulfide bonds. Activins are produced in a variety of tissues while inhibins (α/β dimers) are largely produced in the gonads. Activins are paracrine and autocrine factors throughout the endocrine, reproductive, immune, and hematopoietic systems in adult animals, and are a mesoderm inducer in early development. Activins bind type I and type II serine/threonine kinase receptors to exert pluripotent effects. The actions of activins are modified (in part) by an activin-binding protein (follistatin) and inhibin. This chapter briefly introduces various biological effects of activins, including their signaling pathway.
Placenta derived factors involved in the pathogenesis of the liver in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP): A review
2019, Pregnancy Hypertension
With this review we try to unravel if placenta-derived factors are able to initiate liver sinusoidal endothelial cells (LSEC) decay in HELLP syndrome and eventually cause the development of sinusoidal obstruction syndrome (SOS).
Haemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is a severe complication of pregnancy. It is characterized by elevated liver enzymes, low platelet count and haemolytic anaemia. The risk of developing HELLP syndrome within a pregnancy is 0.1–0.8%. The mortality rate among women with HELLP syndrome is 0–24% and the perinatal death goes up to 37%. The aetiology of HELLP syndrome is not fully understood but the pathogenesis of the liver pathology in the HELLP syndrome resembles that of a SOS with endothelial damage of the LSECs which ultimately leads to liver failure.
We hypothesize that placenta derived factors cause LSEC damage and thereby liver dysfunction.
We searched in the PubMed database for relevant articles about placenta derived factors involved in endothelial activation especially in the liver. We yielded eventually 55 relevant articles.
Based on this literature search we associate that in HELLP syndrome there is an increase of soluble fms-like tyrosine kinase (sFlt1), vascular endothelial growth factor (VEGFR), soluble endoglin (sEng), galectin-1 (Gal-1), endothelin-1 (ET-1), Angiopoietin 2 (Angs-2), Asymmetric dimethylarginine (ADMA), activin B, inhibin A, Fas ligand (FasL) and heat shock protein 70 (Hsp70).
We assume that these eleven increased placenta derived factors are responsible for LSEC damage which eventually leads to liver failure. This concept shows a possible design of the complicated pathophysiology in HELLP syndrome. However further research is required.
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Citation Excerpt :
The subunits βD and βE were isolated from Xenopus and mouse cDNA library, respectively [16,17]. The activin-βE subunit shows close similarity to the activin-βC in terms of genomic organization and chromosomal localization, amino acid sequence and high expression in liver [18]. In 2000 Lau and co-workers cloned and generated mice deficient in the activin-βC and activin-βE genes to study the function of these activin family members.
Transforming growth factor-β (TGF-β) superfamily signaling pathway and its ligands are essential regulators of cellular processes such as proliferation, differentiation, migration, and survival. Alteration of this pathway results in uncontrolled proliferation and cancer progression. This review focuses on a specific member of the TGF-β superfamily: activin-β_C. After its initial discovery, activin-β_C has been considered non-biologically relevant. Therefore, for years several experimental designs have ignored the potential contribution of this molecule to the final biological outcome. Here we focus on recent advances in the activin field, with a particular emphasis on activin-β_C, its antagonistic mechanism, and the physiological relevance of activin-β_C actions in reproductive and cancer biology.
Covering a novel and previously unexplored function of activin-β_C on cancer associated weight loss and muscle metabolism, this review suggests an imminent need to re-evaluate the function of activin-β_C in biological systems and advances the understanding of how activin-β_C antagonizes the activin signaling pathway. Thus, challenging activin biologists to consider the impact of activin-β_C when interpreting their work.
Activin
2015, Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research
Activins are dimeric proteins composed of β_A- and β_A-subunit (activin A), β_B- and β_B-subunits (activin B) or β_A- and β_B-subunits (activin AB). Mature β_A- and β_B-subunits have nine cysteine residues that are required for inter- and intramolecular disulfide bond. Activins are produced in a wide range of tissues while inhibins (α/β dimers) are largely produced in gonads. Activins exert pluripotent effects on tissue growth and function by binding specific receptors (type I and type II serine/threonine kinase receptors). However, activin effects are modified (in part) by activin-binding protein (follistatin) and inhibin. This chapter briefly introduces various biological effects of activins including their signaling pathway.
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¹: Address correspondence to: Jeffrey Bonadio, M.D., University of Michigan Medical School, 1198 SE, 300 North Ingalls Building, Ann Arbor, MI 48109-0417. Fax: (313) 936-0669. [email protected].

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Regular ArticleMolecular Cloning of the Mouse Activin βESubunit Gene

Abstract

Regular Article
Molecular Cloning of the Mouse Activin β_ESubunit Gene