TGFB1

Protein TGFB1 map

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

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 EMT  map  / ECM  map
 Survival  map  / WNT_CANONICAL  map

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

TGFB1|​hm2|​active@Extracellular space

References
e_re228( EMT  map ):
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
e_re350( EMT  map ):
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
e_re210( EMT  map ):
PMID:9335507
TGFB rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGFB responses.
e_re353( EMT  map ):
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)
e_re1247( EMT  map ):
PMID:15252039
ID2 is target of HIF1 upon hypoxic conditions
e_re1523( EMT  map ):
PMID:18403754
PMID:16607286


Modifications:
In compartment: Extracellular space
  1. TGFB1|​hm2|​active@Extracellular space map

Participates in complexes:
In compartment: Cytoplasm

  1. TGFB1:​TGFBR*@Cytoplasm map

  2. TGFB1|​hm2:​TGFBR2|​hm2@Cytoplasm map
  3. TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map
  4. E-Cadherin*|​S840_pho|​S853_pho|​S855_pho|​S849_pho:​TGFB1:​TGFBR*@Cytoplasm map
  5. TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map
  6. Occludin*:​PARD6A:​TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map
  7. Occludin*:​PARD6A|​S345_pho:​TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map

In compartment: Early Endosome

  1. SARA*:​TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Early Endosome map

In compartment: Endosome

  1. E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​p120*@Endosome map

  2. E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​_beta_-Catenin*|​pho:​p120*@Endosome map
  3. E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​_beta_-Catenin*|​Y654_pho|​pho:​p120*@Endosome map

In compartment: Extracellular space

  1. Latency-associated protein*:​TGFB1@Extracellular space map

  2. Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  3. Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  4. LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  5. Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  6. Actin cytoskeletal*:​Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map

Participates in reactions:
As Reactant or Product:

  1. TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map map TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map

  2. TGFB1|​hm2|​active@Extracellular space map + TGFBR2|​hm2@Cytoplasm map map TGFB1|​hm2:​TGFBR2|​hm2@Cytoplasm map
  3. TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map + ATP@Extracellular space map map TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map + ADP@Extracellular space map
  4. Latency-associated protein*|​hm2@Extracellular space map + TGFB1|​hm2|​active@Extracellular space map map Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  5. Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map + LTBP1@Extracellular space map map LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  6. Integrin A8B1_AVB1_AVB5_AVB6_AVB8*@Extracellular space map + LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map map Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  7. Actin cytoskeletal*@Cytoplasm map + Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map map Actin cytoskeletal*:​Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  8. Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map map Latency-associated protein*|​hm2@Extracellular space map + TGFB1|​hm2|​active@Extracellular space map
  9. TGFB1|​hm2:​TGFBR2|​hm2@Cytoplasm map + TGFBR1|​hm2@Cytoplasm map map TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map
  10. LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map map TGFB1|​hm2|​active@Extracellular space map + LTBP1:​Latency-associated protein*|​hm2@Extracellular space map
  11. SARA*@Early Endosome map + TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map map SARA*:​TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Early Endosome map
  12. Latency-associated protein*:​TGFB1@Extracellular space map map Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map
  13. Occludin*:​PARD6A:​TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map + ATP@Cytoplasm map map Occludin*:​PARD6A|​S345_pho:​TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map + ADP@Cytoplasm map
  14. Occludin*:​PARD6A:​TGFBR1|​hm2@Cytoplasm map + TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map map Occludin*:​PARD6A:​TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map
  15. Occludin*:​PARD6A|​S345_pho:​TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map + SMURF1@Cytoplasm map map PARD6A|​S345_pho:​SMURF1@Cytoplasm map
  16. Actin cytoskeletal*:​Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map map Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2@Extracellular space map + TGFB1|​hm2|​active@Extracellular space map
  17. Cytoskeleton:​E-Cadherin*|​S840_pho|​S853_pho|​S855_pho|​S849_pho:​ECM or cell-cell contact@Cytoplasm map + TGFB1:​TGFBR*@Cytoplasm map map E-Cadherin*|​S840_pho|​S853_pho|​S855_pho|​S849_pho:​TGFB1:​TGFBR*@Cytoplasm map + ECM or cell-cell contact@default map
  18. E-Cadherin*|​S840_pho|​S853_pho|​S855_pho|​S849_pho:​TGFB1:​TGFBR*@Cytoplasm map map E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​_beta_-Catenin*|​pho:​p120*@Endosome map
  19. TGF_beta_ pathway@Cytoplasm map map TGFB1:​TGFBR*@Cytoplasm map
  20. E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​_beta_-Catenin*|​pho:​p120*@Endosome map map E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​_beta_-Catenin*|​Y654_pho|​pho:​p120*@Endosome map
  21. E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​_beta_-Catenin*|​Y654_pho|​pho:​p120*@Endosome map map E-Cadherin*:​ITGA3:​TGFB1:​TGFBR*:​p120*@Endosome map + _beta_-Catenin*|​Y654_pho@Cytoplasm map
  22. TGFB1:​TGFBR*@Cytoplasm map map SMAD2|​pho@Nucleus map

As Catalyser:

  1. TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map + ATP@Extracellular space map map TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map + ADP@Extracellular space map

  2. gID2@Nucleus map map rID2@Nucleus map
  3. SHC1_p66_p52*@Cytoplasm map map SHC1_p66_p52*|​Y_pho|​S_pho|​active@Cytoplasm map
  4. gID3@Nucleus map map rID3@Nucleus map
  5. TRAF6@Cytoplasm map map TRAF6|​ubi|​hm2|​active@Cytoplasm map
  6. gPDGFA@Nucleus map map rPDGFA@Nucleus map
  7. gPDGFR family*@Nucleus map map rPDGFR family*@Nucleus map
  8. gSMAD7@Nucleus map map rSMAD7@Nucleus map
  9. SARA*:​SMAD2@Early Endosome map + ATP@Cytoplasm map map SARA*:​SMAD2|​S467_pho|​S465_pho@Early Endosome map + ADP@Cytoplasm map
  10. SARA*:​SMAD3@Early Endosome map + ATP@Cytoplasm map map SARA*:​SMAD3|​S423_pho|​S425_pho@Early Endosome map + ADP@Cytoplasm map
  11. Occludin*:​PARD6A:​TGFB1|​hm2:​TGFBR1|​hm2:​TGFBR2|​hm2@Cytoplasm map + ATP@Cytoplasm map map Occludin*:​PARD6A|​S345_pho:​TGFB1|​hm2:​TGFBR1|​Ser_pho|​hm2:​TGFBR2|​Ser_pho|​hm2@Cytoplasm map + ADP@Cytoplasm map
  12. gETS1@Nucleus map map rETS1@Nucleus map
  13. SRC@Cytoplasm map map SRC@Cytoplasm map

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