Account : TGF-beta (Transforming Growth Factor beta)

TGF-beta(Transforming Growth Factor beta)

Synonym:

Aqueous humor lymphocyte inhibitory activity
CIF-A ( cartilage inducing factor A =TGF-beta-1 )
CIF-B ( cartilage inducing factor B =TGF-beta-2 )
Corneal epithelial inhibitor of stromal cell collagenase synthesis ( TGF-beta-2 )
DIF ( differentiation-inhibiting factor )
DSF ( decidual suppressor factor =TGF-beta-2 )
EIF ( Epstein-Barr virus inducing factor )
Epithelial cell growth inhibiting factor
G-TsF ( glioma-derived T-cell suppressor factor )
ISF ( immunosuppressive factor =TGF-beta-1 )
MDGF ( milk-derived growth factor )
MGF ( milk growth factor )
MGF-a ( milk growth factor =TGF-beta-2 )
MGF-b ( milk growth factor =TGF-beta-1 )
PDGI ( platelet-derived endothelial cell growth inhibitor =TGF-beta-1 )
Polyergin
Simian BSC-1 cell growth inhibitor
SP factor
TCGF ( transformed cell growth factor )
TGI ( tissue-derived growth inhibitor )
TIF-1 ( tumor inducing factor-1 ).

Structure/Function

Depending upon cell type or conditions, the secretion of TGF-beta can be induced by a number of different stimuli including steroids, retinoids, EGF , NGF , activators of lymphocytes , vitamin D3 , and IL1 . The synthesis of TGF-beta can be inhibited by EGF , FGF ,dexamethasone, calcium , retinoids and follicle stimulating hormone .TGF-beta also influences the expression of its own gene and this may be important in Wound healing .

TGF-beta can exist associated with the extracellular matrix as a complex with betaglycan and decorin. This allows the factor to be stored in a biologically inactive form. The exact molecular mechanisms underlying its release from these reservoirs is unknown.

Protein characteristics :

TGF-beta exists in at least five isoforms, known as TGF-beta-1 , TGF-beta-2 , TGF-beta-3 , TGF-beta-4 , TGF-beta-5 , that are not related to TGF-alpha . Their amino acid sequences display homologies on the order of 70-80 %.TGF-beta-1 is the prevalent form and is found almost ubiquitously while the other isoforms are expressed in a more limited spectrum of cells and tissues. TGF-beta-2 , NGF , and PDGF-BB share a similar overall topology.

The biologically active forms of all isoforms are disulfide-linked homodimers. Disulfide-linked heterodimers of TGF isoforms have been reported also. The heat- and acid-stable monomeric subunits have a length of 112 amino acids. TGF-beta-4 contains two additional amino acids in the vicinity of the aminoterminal end.

The isoforms of TGF-beta arise by proteolytic cleavage of longer precursors ( TGF-beta-1 : 390 amino acids, TGF-beta-2 : 412 amino acids, TGF-beta-3 : 412 amino acids, TGF-beta-4 : 304 amino acids, TGF-beta-5 : 382 amino acids). The isoforms are derived from the carboxyterminal ends of these precursors.

The mechanisms of TGF-beta activation are not known in detail. The main fraction of the factor in the serum is covalently attached to one of the Acute phase proteins , Alpha-2-Macroglobulin (alpha2M) the synthesis of which is known to be induced several hundred-fold by IL6 . Alpha2M/TGF-beta complexes are believed to represent TGF-beta molecules released by platelets after tissue injuries and destined to degradation (see also: Inflammation , Wound healing ).

Gene structure :

The different isoforms of TGF-beta are encoded by different genes. All genes have a length of more than 100 kb and contain seven exons. The genes map to different chromosomes. The TGF-beta-1 gene maps to human chromosome 19q13; the TGF-beta-2 gene maps to human chromosome 1q41; the TGF-beta-3 gene maps to human chromosome 14q24. These genes are differentially expressed. The TGF-beta-3 gene is strongly expressed in embryonic heart and lung tissues but only marginally in liver, spleen, and kidney tissues. TGF-beta-1 is strongly expressed in spleen tissues.

Related factors :

TGF-beta is the prototype of a family of proteins known as the TGF-beta superfamily. This family includes Inhibins , Activin A , MIS (Mlerian inhibiting substance ), BMP(bone morphogenetic proteins ), dpp (decapentaplegic ) and Vg-1 . MNSF (monoclonal nonspecific suppressor factor ) shows 60 %sequence identity with TGF-beta-2 .

Biological activities :

The biological activities of TGF-beta are not species-specific. The various TGF-beta isotypes share many biological activities and their actions on cells are qualitatively similar in most cases although there are a few examples of distinct activities. In some systems TGF-beta-3 appears to be more active than the other isotypes. TGF-beta-2 is the only variant that does not inhibit the growth of endothelial cells. TGF-beta-2 and TGF-beta-3 , but not TGF-beta-1 , inhibit the survival of cultured embryonic chick ciliary ganglionic neurons. The most pronounced differences in the TGF-beta isoforms is their spatially and temporally distinct expression of both the mRNAs and proteins in developing tissues, regenerating tissues, and in pathologic responses.

GenBank (through Genome Net)

Sequence Information

Journal Information

last updated 21/05/98