Expression and dimerization of the rat activin subunits betaC and betaE: evidence for the ormation of novel activin dimers

Abstract

Activins are cytokines of the transforming growth factor β family, which plays a central role in the determination of cell fate and the regulation of tissue balance. Family members are composed of two subunits and this dimerization is critical for liganding their cognate receptors and execution of proper functions. In the current study we focused on the localization of activin β A , β B , β C and β E subunits in the adult rat and analyzed the composition of putative activin β dimers. By dissecting tissue distribution of various activins, we found that the liver, in particular the hepatocytes, is the major source for activin β C and β E transcripts, since other tissues almost failed to express these isoforms. In sharp contrast, the emergence of activin β A and β B appeared ubiquitous. Using a highly selective proteome approach, we were able to identify homo-as well as heterodimers of individual activin subunits, indicating a high redundancy of ligand composition. Certainly, this broad potential to homo-and heterodimerize has to be considered in future studies on activin function.

Activins and activin antagonists in hepatocellular carcinoma

“…Concerning the liver, the role of the βB subunit is not well characterized. In the normal rat liver the βB subunit was the only activin subunit undetectable by RNAse protection assay [14] . Weak positive immunoreactivity for βB was, however, detected in hepatocytes of normal A B (3) rat livers and in connective tissue septa in fibrotic livers when analyzed by immunohistochemistry [55] .…”

“…Activin terminology is dependent on the dimer configuration with a single letter designating homodimers (activins A, B, C, and E) and two letters designating heterodimers according to their subunit composition (activins AB, AC, AE, BC etc.). With respect to tissue expression, transcripts of the βA and βB subunits were found to be detectable in almost all tissues analyzed with especially high expression in reproductive organs [13,14] . The βC and βE subunits, in contrast, are predominantly expressed in the liver and at lower levels in a limited number of additional organs [14][15][16][17][18] .…”

“…With respect to tissue expression, transcripts of the βA and βB subunits were found to be detectable in almost all tissues analyzed with especially high expression in reproductive organs [13,14] . The βC and βE subunits, in contrast, are predominantly expressed in the liver and at lower levels in a limited number of additional organs [14][15][16][17][18] . Activin β subunits are synthesized as precursor molecules with 350-426 amino acids and molecular weights between 38 kDa and 50 kDa [19] .…”

“…Activin βB Like activin βA, the βB subunit is expressed in multiple tissues and organs [13,14] . Despite a considerable overlap in tissue expression and in some biological activities, important differences exist [64] .…”

Inhibin, activin, follistatin and FSH serum levels and testicular production are highly modulated during the first spermatogenic wave in mice

“…Activin and inhibin are members of the transforming growth factor-b (TGF-b) superfamily that were initially identified by their ability to regulate FSH secretion at the pituitary. FSH regulates Sertoli cell function directly and germ cell development indirectly (reviewed in de Mather et al 1997 (Yu et al 1994, Vihko et al 1998, O'Connor et al 1999, Mellor et al 2000, Muttukrishna et al 2000, Vejda et al 2002.…”