Transforming growth factor
From Wikipedia, the free encyclopedia
Transforming growth factor (TGF) is used to describe two classes of polypeptide growth factors, TGFα and TGFβ. These proteins were originally characterized by their capacity to induce oncogenic transformation in a specific cell culture system, rat kidney fibroblasts. Application of the transforming growth factors to normal rat kidney fibroblasts induces the cultured cells to proliferate and overgrow, no longer subject to the normal inhibition caused by contact between cells.
The name "Transforming Growth Factor" is somewhat arbitrary, since the two classes of TGFs are not structurally or genetically related to one another, and they act through different receptor mechanisms. Furthermore, they do not always induce cellular transformation, and are not the only growth factors that induce cellular transformation.
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[edit] TGFα
TGFα is upregulated in some human cancers. It is produced in macrophages, brain cells, and keratinocytes, and induces epithelial development. It is closely related to EGF, and can also bind to the EGF receptor with similar effects . TGFα stimulates neural cell proliferation in the adult injured brain [2].
TGFα was cited in the 2001 NIH Stem Cell report to the U.S. Congress as promising evidence for the ability of adult stem cells to restore function in neurodegenerative disorders.
[edit] TGFβ
TGFβ exists in at least three known subtypes in humans, TGFβ1, TGFβ2, and TGFβ3. These are upregulated in some human cancers, and play crucial roles in tissue regeneration, cell differentiation, and embryonic development. TGFβ1 frequently exerts a growth inhibitory role on epithelial cells, becoming expressed at high levels late in regenerative processes as cell division comes to an end. The TGFβ superfamily includes other homologous ligands including activin and bone morphogenetic proteins.
[edit] The TGFβ receptor
TGFβ receptors are single pass serine/threonine kinase receptors. They exist in several different isoforms that can be homo- or heterodimeric [3]. The number of characterized ligands in the TGFβ superfamily far exceeds the number of known receptors, suggesting the promiscuity that exists between the ligand and receptor interactions.
TGF can be found in many different tissue types, including brain, heart, kidney, liver and testes. Over-expression of TGF can induce renal fibrosis, causing kidney disease, as well as diabetes, and ultimately end-stage renal disease (ESRD). Recent developments have found that, using certain types of protein antagonists against TGFβ receptors, can halt and in some cases reverse the effects of renal fibrosis.
[edit] References
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New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci USA. 1981 Sep; 78(9): 5339-43; PubMed Free text - a In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci USA. 2000 Dec 19; 97(26): 14686-91; PubMed Free text
- a Heteromeric and homomeric transforming growth factor-beta receptors show distinct signaling and endocytic responses in epithelial cells. J Biol Chem. 1998 Nov 27; 273(48): 31770-7; PubMed Free text
[edit] See also
| Cell signaling |
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| Key concepts - Ligand | Receptor | Second messenger | Protein kinase | Transcription factor | Cell signaling networks |
| Pathways - Apoptosis | Ca2+ signaling | Cytokine signaling | Hedgehog | Integrin signaling | JAK/STAT | Lipid signaling | MAPK/ERK pathway | mTOR | NF-kB | Notch | p53 | TGFβ | Wnt |
