Identifiers
transforming growth factor beta receptor 1
HUGO:TGFBR1 hgnc_id:HGNC:11772 HGNC:11772 ENTREZ:7046 UNIPROT:P36897
HUGO:TGFBR1, HGNC:11772, ENTREZ:7046, UNIPROT:P36897, GENECARDS:GC09P101867
HUGO:TGFBR1
"transforming growth factor beta receptor I (activin A receptor type II-like kinase 53kD)"
HUGO:TGFBR1 HGNC:11772 ENTREZ:7046 UNIPROT:P36897
Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / GROWTH_FACTORS_SIGNALING_PATHWAYS
EMT Senescence / EMT_REGULATORS
EMT Senescence / ECM
Innate Immunity / IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
References
PMID:24132110, PMID:15265520
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:20519943
PMID:17934056
PMID:16474430
PMID:14557817
PMID:24132110
TGF-beta is known to cause a hetero-oligomerisation of the TGFBR1/TGFBR2 complex consisting of two TGFBR1 and two TGFBR2 molecules to activate it (not modelled).
Besides cellular stresses the SAPK pathways are also activated by cytokines such as TGF-beta. Smad-dependent gene expression can provoke P38 activation in response to TGFbeta.
PMID:20060931 PMID:21614932
References
em_emtc_emtc_re340( EMT Senescence ):
PMID:15761153
Occludin is a structural component of tight junctions that is associated with the cell polarity network.
Occludin regulates TGFBR1 localization for efficient TGFB-dependent dissolution of tight junctions during EMT
Interaction of endogenous OCLN with endogenous TGFBR1 was not modulated by TGFB
but its association with the TGFBR2 increased in a TGFB-dependent manner
PMID:15761148
TGFBR1 localizes with ZO-1 on the cellular apical aspect together with PARD6A and they are situated apically to endogenous E-cadherin
After stimulation by TGFB, TGFBR2 is redistributed to the tight junctions, where it localizes with both TGFBR1 and ZO-1.
em_emtc_emtc_re1166( EMT Senescence ):
PMID:22286770
The inhibitory Smad7 mRNA is repressed by MIR106B, MIR93, MIR25.
Smad7 antagonizes TGF-b signaling through multiple mechanisms, including binding to TGFBR1 and interfering with recruitment and downstream phosphorylation and activation of Smad2 and Smad3.
Smad7 also functions to recruit E3 ubiquitin ligases to TGRFBR1, resulting in its degradation.
Repression of Smad7 therefore activates TGF-beta signaling.
em_emtc_emtc_re1167( EMT Senescence ):
PMID:11278251
Inhibitory Smad7 associates with Smurf1 in the nucleus and is exported to the cytoplasm.
Smad7 thus recruits Smurf1 to TGFBR1, resulting in the degradation and rapid turnover of the TGFBR1 protein.
References
em_emtc_emtc_re1167( EMT Senescence ):
PMID:22286770
The inhibitory Smad7 mRNA is repressed by MIR106B, MIR93, MIR25.
Smad7 antagonizes TGF-b signaling through multiple mechanisms, including binding to TGFBR1 and interfering with recruitment and downstream phosphorylation and activation of Smad2 and Smad3.
Smad7 also functions to recruit E3 ubiquitin ligases to TGRFBR1, resulting in its degradation.
Repression of Smad7 therefore activates TGF-beta signaling.
PMID:11278251
Inhibitory Smad7 associates with Smurf1 in the nucleus and is exported to the cytoplasm.
Smad7 thus recruits Smurf1 to TGFBR1, resulting in the degradation and rapid turnover of the TGFBR1 protein.
+ TGFBR2@Cytosol + TGFB*@default → TGFB*:TGFBR1:TGFBR2@Cytosol
→ degraded
→ TGFBR1@Cytosol
+ SMAD7@Cytosol → em_emtc_emtc_s3754
→ TGFBR1|ubi|hm2@Cytosol
→ degraded
→ TGFBR1|hm2@Cytosol
→ TGFB1|hm2:TGFBR1|hm2:TGFBR2|hm2@Cytosol
+ ATP@Extracellular space → TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Cytosol + ADP@Extracellular space
+ TGFBR1|hm2@Cytosol → TGFB1|hm2:TGFBR1|hm2:TGFBR2|hm2@Cytosol
+ TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Cytosol → SARA*:TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Early Endosome
+ TGFBR1|hm2@Cytosol + Occludin*@Cytosol → Occludin*:PARD6A:TGFBR1|hm2@Cytosol
+ ATP@Cytosol → Occludin*:PARD6A|S345_pho:TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Cytosol + ADP@Cytosol
+ TGFB1|hm2:TGFBR1|hm2:TGFBR2|hm2@Cytosol → Occludin*:PARD6A:TGFB1|hm2:TGFBR1|hm2:TGFBR2|hm2@Cytosol
+ TGFBR2@INNATE_IMMUNE_CELL_Membrane + TGFB*@default → TGFB*:TGFBR1:TGFBR2@INNATE_IMMUNE_CELL_Membrane
+ TAB*@Cytoplasm → TAB*:TGFBR1:TGFBR2@Plasma Membrane
+ TAB*:TGFBR1:TGFBR2@Plasma Membrane → TAB*:TAK1*|pho:TGFBR1:TGFBR2@Cytoplasm
→ rTGFB*@Cytosol
→ SMAD3|pho@Cytosol
→ SMAD2|pho@Cytosol
→ rEGF@Cytosol
+ ATP@Extracellular space → TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Cytosol + ADP@Extracellular space
→ SHC1_p66_p52*|Y_pho|S_pho|active@Cytosol
→ TRAF6|ubi|hm2|active@Cytosol
+ ATP@Cytosol → SARA*:SMAD2|S467_pho|S465_pho@Early Endosome + ADP@Cytosol
+ ATP@Cytosol → SARA*:SMAD3|S423_pho|S425_pho@Early Endosome + ADP@Cytosol
+ ATP@Cytosol → Occludin*:PARD6A|S345_pho:TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Cytosol + ADP@Cytosol
→ rCCL5@INNATE_IMMUNE_CELL_Cytosol
→ SMAD3|pho@INNATE_IMMUNE_CELL_Cytosol
→ SMAD2|pho@INNATE_IMMUNE_CELL_Cytosol
→ O_sub_2_endsub__super_-_endsuper_@INNATE_IMMUNE_CELL_Cytosol
→ rCCL3@INNATE_IMMUNE_CELL_Cytosol
→ rCCL2@INNATE_IMMUNE_CELL_Cytosol
→ MAP2K4|pho|pho@Cytoplasm
→ MAP2K6|pho|pho@Cytoplasm
+ SMAD4@Cytoplasm → su_mpk1_mpk1_s1028
+ SMAD4@Cytoplasm → su_mpk1_mpk1_s1027