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Activin beta-B (inhibin B, activin AB beta polypeptide)Activin-B is the homodimer of the INHBB gene product inhibin/activin beta-B chain. The human gene INHBB (map locus Entrez/HGNC 2cen-q13; Ensembl 2q14.2) gene product is a 407 AA long (45.1 kDa) precursor protein that contains a 28 AA single sequence (1-28), a 264 AA propeptide sequence (29 to 292) and a 115 AA (15 kDa) inhibin/activin subunit B (293 to 407), Mason AJ, et al. (1989). The precursor contains an N-linked glycosylation site at Asn93. The subunit contains four potential disulfide intra-chain bridges (296-304; 303-372; 332-404; 336-406) and a potential inter-chain disulfide bridge at Cys371. Activin B and TGF-beta 1 are structurally related disulfide-linked homodimers synthesized with large precursors. Activin B is a 25.9 kDa homodimer composed of two 15.2 kDa activin beta-B monomers, Schmelzer CH, et al. (1990). Activin-B is involved in the regulation of a variety of cell functions that overlap the actions of activin-A; however, activin-B also regulates many processes that are distinct from activin-A activities. The functional differences between activin-A and activin–B have recently been reviewed, Thompson TB, et al. (2004). Similar to activin-A, activin-B modulates follicle stimulating hormone (FSH) secretion and hemoglobin synthesis, DePaolo LV, et al. (1992); Mason AJ, et al. (1989). It is involved in regulation of the menstrual cycle, Liu J, et al. (2001). Activin-B is not essential for embryo development or survival, but it does have important roles in development. It stimulates spermatogonial proliferation, Mather JP, et al. (1990) and is localized in specific cells, gonocytes and interstitial Leydig cells, and tissues, rete testis and epididymal epithelium, associated with human testis duct system development, Anderson RA, et al. (2002). Activin-B is found in follicle cells surrounding oocytes, Dohrmann CE, et al. (1993) and been shown to increase the rate of oocytes maturation in a dose and time dependent manner, Pang Y and Ge W. (1999, 2002). It is required for successful mammogenesis leading to lactation, Robinson GW and Hennighausen L. (1997). Recent studies suggest that activin-B may regulate adipocyte differentiation, Kogame, M, et al. (2006). Activin-B has been linked to several aspects of embryo development. Activin-B is first detected in blastula-stage embryos, Thomsen G, et al. (1990) after midblastula transition and homogeneously distributed during blastula and early gastrula stages. It becomes restricted to the dorso-anterior region in neurula-stage embryos and by early tailbud stage it is restricted to brain, eye anlagen, visceral pouches, otic vesicles and the anterior notochord, Dohrmann CE, et al. (1993). Activin-A and -B localizations are different in 3.5 and 4.5 day mouse blastocyst, Paulusman CC, et al. (1994). Nakamura, T et al. (1992) suggested that the primary function of Activin-B may involve mesoderm-inducing activity and early development modulation. Schrewe H, et al (1994) and Vassalli A, et al. (1994), reported that activin-B was not essential for survival or for mesoderm formation (in mouse), but that it played a role in late fetal development and female fecundity. A role for activin-B in axial formation was suspected because ectopic expression produced second body axis embryos, Thomsen G, et al. (1990), Mitrani E, et al. (1990). The roles of activin-B during embryo development are starting to emerge. Activin-B may modulate gap junction permeability in embryos, Olson DJ and Moon RT. (1992). Activin-B has been shown to modulate the morphogenesis of the roof plate (RP) of midbrain wherein it inhibits roof plate differentiation, Alexandre P, et al. (2006). Activin-B signals cell cycle arrest in cells of the involuting dorsal axial mesoderm, Ramis JM, et al. (2007). Activin-B is involved in the development of the adrenal gland and pancreas. It is present in normal adrenal medulla, but absent in the cortex, Salmenkivi K et al. (2001). Interestingly, Activin-B may be a marker for benign adrenal pheochromocytomas, Salmenkivi K et al. (2001). The role of activin-B in pancreas development is of particular interest because of efforts to use human embryonic stem cells (hESC) as precursors to make insulin producing cells for treatment of diabetes. Activin-B has been shown to promote expression of the pancreas marker Pdx1 gene in cells of differentiated embryoid bodies (EB), in culture, Frandsen U, et al. (2007). Most recently, Jafary H, et al. (2008) induced insulin-secreting cells for ES by adding activin-B to nestin-positive selection protocol cells. Sigma offers antibodies and shRNAs useful for the study of Activin B.. References: Alexandre P, et al. (2006) Positive and negative regulations by FGF8 contribute to midbrain roof plate developmental plasticity. Development. 133: 2905-2913. |
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