TGFB*

Protein TGFB*

Identifiers
transforming growth factor beta 1
HUGO:TGFB1 hgnc_id:HGNC:11766 HGNC:11766 ENTREZ:7040 UNIPROT:P01137
transforming growth factor beta 2
HUGO:TGFB2 hgnc_id:HGNC:11768 HGNC:11768 ENTREZ:7042 UNIPROT:P61812
transforming growth factor beta 3
HUGO:TGFB3 hgnc_id:HGNC:11769 HGNC:11769 ENTREZ:7043 UNIPROT:P10600
HUGO:TGFB1 HUGO:TGFB2 HUGO:TGFB3

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / GROWTH_FACTORS_SIGNALING_PATHWAYS
Cancer Associated Fibroblasts / GROWTH_FACTORS_PRODUCTION
Cancer Associated Fibroblasts / TREG_MODULATORS
Innate Immunity / IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS
Innate Immunity / TUMOR_GROWTH

References
CASCADE:TNF
PMID:21098712
Cancer TGFB exosomes trigger fibroblast to myofibroblast differentiation
PMID:15653932
Treatment of fibroblasts with TNF-?? resulted in a significant increase in TGF-??1 protein as measured by ELISA. The increase in protein was preceded by a 200???400% increase in TGF-??1 mRNA detected by quantitative, real-time, reverse transcriptase???polymerase chain reaction. Western blot analysis showed that TNF-?? activated the extracellular signal???regulated kinase (ERK), and inhibitors of the ERK-specific mitogen-activated protein kinase pathway (PD98059 or U0126) blocked TNF-?? induction of TGF-??1
PMID:23784029, PMID:16572188, PMID:8515656
TGF-??1 treatment successfully transformed primary resting fibroblasts into CAFs
PMID:19038247
TGFbeta induces fibroblast collagen biosynthesis downstream of CCL7 and via SMAD3.
Thus, ERK, a MAPK family member, phosphorylates serine residues in the linker regions of Smad1???3 and ERK inhibition reduces TGF??-stimulated Smad phosphorylation as well as collagen biosynthesis, suggesting that ERK activation is necessary for an optimal response to TGF?? [9]. Similarly, p38 MAPK has been shown to be central to TGF?? mediated-collagen and fibronectin expression in SSc fibroblasts [10].
PMID:19747910
Through paracrine signaling molecules, TGF-beta and IL-1beta, cancer cells activate stromal fibroblasts and induce the expression of fibroblast activation protein (FAP). FAP, in turn, affects the proliferation, invasion and migration of the cancer cells. We report that TGF-beta and IL-1beta are important factors in inducing differentiation of myofibroblasts and expression of functional markers, notably alpha-SMA.
PMID:18423981
Differential impact of TGF-beta and EGF on fibroblast differentiation and invasion reciprocally promotes colon cancer cell invasion.
PMID:23034983
Inhibition of TGF-beta/Smad signaling by BAMBI blocks differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and abolishes their protumor effects
PMID:21041659
Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts
PMID:17768418
TGFbeta is responsible for skin tumour infiltration by macrophages enabling the tumours to escape immune destruction.
TGFbeta-mediated tumour progression was accompanied by an increase in tumour-associated macrophages (TAM) and a decrease in tumour-infiltrating dendritic cells (DCs).
???
both TGF-??1 and TGF-??2 are up-regulated in CAFs
PMID:15265520 , PMID:11279127
TGF/SMAD pathway regulates genes involved in extracellular matrix remodeling
PMID:15003992
TGF-??-mediated myofibroblast differentiation and proliferation of the NRK fibroblasts are mutually exclusive responses to TGF-??. Differentiation into myofibroblasts appears to be the default pathway whereas proliferation becomes the dominant and sole response when both TGF-?? and EGF are present.
TGF-?? induced a strong activation of RhoA and stress fiber formation in fibroblasts,
PMID:17979848
TGF-?? promotes the generation and function of Treg cells
TGF-?? is able to convert CD4+CD25??? non-Treg cells into CD4+CD25+ Treg cells, and this conversion was accompanied with increased Foxp3 expression
PMID:26201938
The expression levels of cytokine genes, including those for IL6, CXCL8, TNF, TGFB1, and VEGFA, were higher in CAFs. T cell proliferation was suppressed more by CAFs or their supernatants than by NFs.
PMID:22874531
TGFB treatment induces the autophagy-mediated downregulation of Cav-1 in fibroblasts.
MACROPHAGE
MDSC
NATURAL_KILLER
DENDRITIC_CELL
MAST_CELL
NEUTROPHIL
CASCADE:TGFB
CASCADE:STING
CASCADE:STAB2
CASCADE:TLR2_4
CASCADE:IFNG
PMID:24132110
TGFB has been identified as a factor that inhibits the functional maturation of this cell population9. Immature NK cells do not respond to foreign antigens, thus exposure of NK cells to TGF?? will impair the recognition and the clearance of tumour cells. The inhibition of maturation also prevents the systemic effects of NK cells,
for example, activation of antigen-presenting dendritic cells and inhibition of interferon-?? (IFN??) secretion, which drives T helper 1 cell (TH1 cell) maturation
TGFB1, TGFB2, TGFB3 ligands bind to the type 2 TGF?? receptor (TGFBR2), which causes recruitment and phosphorylation of TGFBR1, resulting in downstream signalling activation.
PMID:17070508, PMID:18490733
TGFB downregulates NKG2D expression.
IL-2/IL-18 prevent the down-modulation of NKG2D by TGF-?? in NK cells via the c-Jun N-terminal kinase (JNK) pathway
PMID:2871107
Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.
PMID:20538542
TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.
The roles of TGF?? in the tumour microenvironment.
PMID:20616810
The polarization of immune cells in the tumour environment by TGFbeta.
PMID:22703233
TGFB1 participates in M2 activation.
PMID:7594497
TGFB1 upregulates IL10 expression in macrophages.
TGFB1 and IL10 dowregulate expression of TNF.
PMID:21278795
TGFB-induced IRAK3 (IRAK-M) expression in tumor-associated macrophages
and inhibit TLR-dependent signaling
PMID:20644162
Cytokine-induced CD33+ human MDSCs have upregulated iNOS, TGF??, VEGF.
PMID:19109155
MDSC inhibit cytotoxicity, NKG2D expression, and IFN-gamma production of NK cells both in vitro and in vivo.
Membrane-bound TGF-beta1 on MDSC is responsible for MDSC-mediated suppression of NK cells.
PMID:21372296
HMGB1 induces the production of angiogenic factors VEGF, and TGFB1 by macrophage via TLR4-dependent mechanisms.
PMID:16424049
IFNG induces INOS and IL10 expression and TGFB secretion in MDSC
PMID:15099563
Mast cells produce cytokines TNF-a, TGF-b, IFN-a, IL-1a, IL-1b, IL-5, IL-6,
IL-13, IL-16, IL-18
PMID:26966341
tudies have shown that, analogously to the M1 and M2 dichotomy, TANs develop a protumorigenic (N2) phenotype in untreated tumors, largely driven by the presence of TGF-??

TGFB*@default

References
in_re423( Innate Immunity ):
PMID:20547845
TLR4 signaling downstream of HMGB1 induces secretion of IL10
PMID:16713974
RNAi-mediated knockdown of CREB, Fos, and Jun expression resulted in diminished TLR2-induced IL-10 production
GSK3B inhitits activation (DNA binding) of AP-1 factors.
JNK is a classical activator of AP1 transcription factors.
Inhibition of JNK downregulates IL10 expression. Probably via
AP1.
PMID:17404308
CSF1 upregulates expression of IL10 and CCL2 probably via CSF1R.
PMID:15749884
c-Maf binds to the ???206/???171 region in the IL-10 promoter and upregulates IL10 expression.
in_re731( Innate Immunity ):
PMID:21278795
TGFB-induced IRAK3 (IRAK-M) expression in tumor-associated macrophages
and inhibit TLR-dependent signaling
in_re1031( Innate Immunity ):
PMID:12907458
Bcl-3??? ???interacted with NF-??B p50,
both Bcl-3??? ???and p50??? ???were recruited to the TNF promoter,
BCL3??? ??? and??? ???p50??? ???NFkB recruitment to??? ???TNF ???promoter
prevents binding of??? ???p65/p50??? ???NFkB??? ???heterodimers
to??? ???TNF promotor and suppresses??? ???TNF ???expression
downstream of??? ???IL10.
PMID:17485448
Inhibition of??? ???NFkB signaling downstream of??? ???ABIN3??? ???
inhibits expression of??? ???IL8,??? ???IL6,??? ???TNF,??? ???IL12.
PMID:15465827
BCL3 forms complex with HDAC1 and
repression of the TNF promoter by BCL3
requires Histone Deacetylase Activity.
BCL3 inhibits expression of TNF.
PMID:11875494
HMOX1 (HO1) mediates IL-10-induced suppression of TNF production.
PMID:16878026, PMID:14660645, PMID:15644117, PMID:10952726
Increased TNF expression downstream of HMGB1 is regulated via MYD88 and probably NFkB.
PMID:10754326
Human TNF-alpha gene has binding sites for NF-kappa B. By transient transfection,
NF-kappa B p65 and p50 synergistically activated the TNF-alpha promoter.
Although both the kappa B1 and kappa B3 sites bound transcriptionally active NF-kappa B p50/p65 heterodimers, only the kappa B1 site contributed to down-regulation by NF-kappa B p50 homodimers.
CSF1 downregulates TNF, IL-23p19, IL-12p40 expression probably via induction of acomulation of p50 homodimer and inhibition of p65/p50 NF-kB signaling.
CSF2 upregulates expression of TNF, and have positive influence on IL12p70 (p40+p35), IL23 (p40+p19) expression, probably via induction rapid IkBa degradetion, RELA nuclear translocation and formation p65/p50 heterodimers provided induction of NFkB signaling.
PMID:7594497
TGFB1 and IL10 dowregulate expression of TNF.
PMID:23390297
MIF inhitits expression of M1 markers such as TNF.

Modifications:
In compartment: INNATE_IMMUNE_CELL_Cytosol

TGFB*@INNATE_IMMUNE_CELL_Cytosol

In compartment: INNATE_IMMUNE_CELL_Membrane

TGFB*@INNATE_IMMUNE_CELL_Membrane

In compartment: default

TGFB*@default

Participates in complexes:
In compartment: INNATE_IMMUNE_CELL_Membrane

TGFB*:TGFBR1:TGFBR2@INNATE_IMMUNE_CELL_Membrane

Participates in reactions:
As Reactant or Product:

As Catalyser: