A new type of transforming growth factor-beta, TGF-beta 3.

Abstract

A new type of TGF‐beta, TGF‐beta 3, has been identified by cDNA characterization. The amino acid sequence of mature TGF‐beta 3 and its precursor has been derived from porcine and human cDNA sequences. The human TGF‐beta 3 gene is spread over seven exons as in the case of the TGF‐beta 1 gene. Comparison with TGF‐beta 1 and ‐beta 2 indicates a strong conservation of the mature sequences, but a relaxed homology in the precursor segments. TGF‐beta 3 mRNA is mainly expressed in cell lines from mesenchymal origin, suggesting a biological role different from the other TGFs‐beta.

Defective cleavage of membrane bound TGFα leads to enhanced activation of the EGF receptor in malignant cells

“…However, signi®cant amounts of the 17-kDa form were still present (*50%) after 4 h chase. This is contrast to TGFa transfected normal cells in which release of the mature TGFa and conversion of the 17-kDa species to the 15-kDa pro- (Baselga et al, 1996;Derynck et al, 1988). The relatively large amount of 17-kDa form remaining after a 4-h chase indicated defective cleavage of membrane bound TGFa in CBS4aS cells.…”

“…It is released from the cell following cleavage from a 160 amino acid transmembrane precursor (Derynck et al, 1988;Gentry et al, 1987;Lee et al, 1985;Mueller et al, 1989). This precursor is glycosylated and palmitoylated and has biological activity (Bringman et al, 1987;Massague, 1990).…”

The role of Smad signaling in hematopoiesis

“…Other key members of this TGF-b superfamily are the activins, BMPs and growth and differentiation factors (Massague, 1998). There are three isoforms of TGF-b in mammals, TGF-b1 (Derynck et al, 1985), TGF-b2 (de Martin et al, 1987;Madisen et al, 1988) and TGF-b3 (Derynck et al, 1988;ten Dijke et al, 1988), which are encoded by separate genes located at different chromosomes. These isoforms share 70-80% amino-acid sequence identity, bind to the same receptors and show very similar actions in in vitro culture systems.…”

The Interaction of the Transforming Growth Factor-βs with Heparin/Heparan Sulfate Is Isoform-specific

“…5). Two specific basic residues, at positions 26 and 60 in both TGF-␤1 (38) and -␤2 (39), are replaced by neutral ones in TGF-␤3 (40). Interestingly, basic residues are also conserved at these positions in TGF-␤4 (41) and -␤5 (42) and, as there are no other such differences in TGF-␤4, and only a single change at residue 110 (a conformationally buried residue) in TGF-␤5, it is likely that these isoforms will also prove to be heparin/HS-binding.…”