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transforming growth factor [TGF]-beta
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:
- epithelial cells
- endothelial cells
- fibroblasts
- neurons
- lymphocytes
- osteoblasts
- hematopoietic cells
- 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:
a) 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
Interactions
molecular events
General
cytokine
oligomerizing protein
regulatory molecule
TGF-beta family protein
transforming growth factor (TGF)
Properties
CONFIGURATION:
dimer
SIZE: MW = 25 kD
entity length = 112 aa
COMPARTMENT:
extracellular compartment
STATE:
active state
MOTIF:
binding site
FOR-BINDING-OF: matrix protein
cysteine-rich region
MOTIF: cysteine residue {X+0}
MODIFICATION: cysteine residue {X+7}
cysteine residue {X+6}
MODIFICATION: cysteine residue {X+50}
cysteine residue {X+7}
MODIFICATION: cysteine residue {X+0}
cysteine residue {X+26}
MODIFICATION: cysteine residue {X+70}
cysteine residue {X+29}
MODIFICATION: cysteine residue {X+72}
cysteine residue {X+49}
MODIFICATION: cysteine residue {X+49}
cysteine residue {X+50}
MODIFICATION: cysteine residue {X+6}
cysteine residue {X+70}
MODIFICATION: cysteine residue {X+26}
cysteine residue {X+72}
MODIFICATION: cysteine residue {X+29}
glutamine-rich region
MOTIF: glutamine residue (6)
SECRETED-BY:
platelet
macrophage
monocyte
T-cell
endothelial cell
fibroblast
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: 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: 1644257
- Henderson B & Blake S
Therapeutic potential of cytokine manipulation
TIPS 13:145 1992
PMID: 1589908
- Ross R
The pathogenesis of atherosclerosis
Nature 362:801 1993
PMID: 8479518
- 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: 11586292
- Yue J, Mulder KM.
Transforming growth factor-beta signal transduction in
epithelial cells.
Pharmacol Ther. 2001 Jul;91(1):1-34. Review.
PMID: 11707292