TGFB1

Protein TGFB1

Identifiers
transforming growth factor, beta 1
HUGO:TGFB1, HGNC:11766, ENTREZ:7040, UNIPROT:P01137, GENECARDS:GC19M041837
HUGO:TGFB1
HUGO:TGFB1 HGNC:11766 ENTREZ:7040 UNIPROT:P01137 GENECARDS:TGFB1 REACTOME:65937 KEGG:7040 ATLASONC:GC_TGFB1 WIKI:TGFB1

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / ECM
HMC:TUMOR_PROMOTING_INFLAMMATION
Innate Immunity / IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_CANONICAL

References
PMID:20519943
PMID:17934056
PMID:16474430
PMID:14557817
PMID:21900405
TGFB inhibits proliferation
TGFB overproduction causes fibrosis.
PMID:15548370
TGFB1 is a prominent EMT-inducing factor.
The induction of EMT by TGFB1 is associated with the activation of JNK, p38, Erk, PI3k???Akt, and RhoA.
Activation of the Erk pathway is required for TGFB1???induced EMT In Vitro
PMID:11133108
C. parvum infection stimulates both IL8, TGFB secretion by both the basal and apical side of caco-2 cells
PMID:19920116
LAP is known to bind to ITG heterodimers and activate TGFB.
LAP and TGFB were also prominently expressed at the basal surface of endometrial epithelia
PMID:19010789
In early stages of carcinogenesis, TGBF has an anti-oncogenic effects:
TGFB inhibits the growth of epithelial cells.
In later stage, sensitivity to these effects of TGFB is frequently lost and TGFB would favor the development of tumors progression and metastasis
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.

TGFB1|hm2|active@Extracellular space

References
em_emtc_emtc_re228( EMT Senescence ):
PMID:21900405
MMP13 activates TGFB by cleavage of LAP
Plasmin activates TGFB by cleavage of LAP
MMP9 activates TGFB by cleavage of LAP
Integrin aVb6 activates the ECM-bound latent TGFB1 and TGFB3 by traction
Integrin aVb8 and MMP14 (so-called MT1-MMP) cooperate to activate the ECM-bound latent TGFB1 and TGFB3:
-Integrin aVb8 binds LAP from the large latent complex
-MMP14 then is recruited to cleave LAP
em_emtc_emtc_re350( EMT Senescence ):
LAP contains an integrin-binding site called RBD
Several RBD-binding integrins are able to activate latnet TGFB complex through binding this site.
PMID:21909923
The previously mentionned integrins are: a8b1, aVb1, aVb5, aVb6, aVb8.
In the complex Ingergin-large latent TGFB complex, I picked aVb6 as example. But a8b1, aVb1, aVb5, and aVb8 can active TGFB with the same mechanism.
Integrin aVb6 activates the ECM-bound latent TGFB1 and TGFB3 by traction, without participation of MMPs, so no hydrolyse or clevage
em_emtc_emtc_re210( EMT Senescence ):
PMID:9335507
TGFB rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGFB responses.
em_emtc_emtc_re353( EMT Senescence ):
PMID:9157999
VEGF increased the level of ETS1 mRNA in human umbifical vein endothelial cells and lung microvascular endothelial cells over 5-fold.
Protein levels were shown to increase concordantly.
PMID:15111329
VEGF induces Ets-1 expression in bovine retinal endothelial cells and its expression is PKC/ERK pathway-dependent.
Ets-1 up-regulation is involved in the development of retinal neovascularization, and inhibition of Ets-1 may be beneficial in the treatment of ischemic ocular diseases
PMID:12490555
Snail is able to induce the expression of Slug and all other neural crest markers (Zic5, FoxD3, Twist and Ets1)
PMID:16716598
PMID:11708773
Endothelin1 is target gene of HIF1
PMID:21041997
In cells induced to undergo EMT, TGFB also activates the expresion of ZEB1 and ZEB2 through upregulation of ETS1 expression, which then may cooperate with the bHLH transcription factor E47 (TCF3)
PMID:17615296
TGFB induces ETS1 transcriptional expression.
TGFB represses ID2 and ID3 transcriptional expression (PMID:15121845 and PMID:15181457)
ID2 may regulate the function of Ets1 to modulate the transcription of ZEB1 and ZEB2 without alteration of the transcription of Ets1.
Ets1 may act as an inducer of ZEB1 in collaboration with E47 (TCF3)
em_emtc_emtc_re1247( EMT Senescence ):
PMID:15252039
ID2 is target of HIF1 upon hypoxic conditions
em_emtc_emtc_re1523( EMT Senescence ):
PMID:18403754
PMID:16607286

Modifications:
In compartment: Extracellular space

TGFB1|hm2|active@Extracellular space

In compartment: INNATE_IMMUNE_CELL_Cytosol

TGFB1@INNATE_IMMUNE_CELL_Cytosol

Participates in complexes:
In compartment: Cytoplasm

In compartment: Cytosol

In compartment: Early Endosome

SARA*:TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Early Endosome

In compartment: Endosome

In compartment: Extracellular space

Participates in reactions:
As Reactant or Product:

As Catalyser: