transforming growth factor [TGF]-beta
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Function
- binds to core protein of matrix proteoglycan decorin
- latent TGF-beta can be activated by plasmin & metalloproteases MMP9 & MMP12[6]
- role in:
- cell proliferation
- differentiation
- embryonic development
- adhesion
- extracellular matrix production
- increases synthesis of collagen, fibronectin, laminin, proteoglycans
- increases expression of protease inhibitors such as plasminogen activator inhibitor-1, TIMPS
- inhibits expression of collagenase, transin, thiol proteinase
- cell motility
- apoptosis
- chemotactic for macrophages
- suppresses various T & B-cell functions (immunosuppressive)
- inhibits mitogenesis of many cell types
- growth inhibition - arrests cells in late G1 phase of cell cycle
- growth inhibitor for:
- phosphorylation of smads by TGF-beta receptors affect signaling.
- TGF-beta also may affect ERK, JNK, p38mapk PI3k & rho GTPases
Structure
- secreted as latent complex comprised of:
- latent TGF-beta binding protein b0 latency-associated peptide (N terminal prodomain of TGF beta)
Compartment
- sequestered to the extracellular matrix
Expression
- all immune cells (B-cells, T-cells, monocytes/macrophages, dendritic cells) secrete TGF-beta
Pathology
- function compromised in some cancers
Genetics
- 5 different subtypes derived from at least 3 distinct genes
More general terms
- transforming growth factor (TGF)
- TGF-beta family protein
- cytokine
- oligomerizing protein
- regulatory molecule
More specific terms
- smad induced genes/smad gene targets
- transforming growth factor beta-1; TGF-beta-1; contains: latency-associated peptide; LAP (TGFB1 TGFB)
- transforming growth factor beta-2; TGF-beta-2; BSC-1 cell growth inhibitor; Cetermin; Glioblastoma-derived T-cell suppressor factor; G-TSF; polyergin (TGFB2)
- transforming growth factor beta-3; TGF-beta-3 (TGFB3)
- transforming growth factor beta-4; Left-right determination factor 2; endometrial bleeding-associated factor; Left-right determination factor A; protein lefty-2; protein lefty-A; TGF-beta-4 (LEFTY2, EBAF, LEFTA, LEFTYA, TGFB4, PSEC0024)
Additional terms
References
- ↑ Sporn MB, Roberts AB. Interactions of retinoids and transforming growth factor-beta in regulation of cell differentiation and proliferation. Mol Endocrinol. 1991 Jan;5(1):3-7. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2017191
- ↑ Primary Hyperlipoproteinemias, Steiner & Shafrir (eds), McGraw Hill, NY, 1991, pg 89
- ↑ Hajjar DP & Pomerantz KB Signal transduction in atherosclerosis: integration of cytokines and the eicosanoid network. FASEB J 6:2933 1992 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1644257
- ↑ Henderson B & Blake S Therapeutic potential of cytokine manipulation TIPS 13:145 1992 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1589908
- ↑ Ross R The pathogenesis of atherosclerosis Nature 362:801 1993 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8479518
- ↑ 6.0 6.1 Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 2001 Oct;29(2):117-29. Review. Erratum in: Nat Genet 2001 Nov;29(3):351. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11586292
- ↑ Yue J, Mulder KM. Transforming growth factor-beta signal transduction in epithelial cells. Pharmacol Ther. 2001 Jul;91(1):1-34. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11707292