Phospho-TGFBR1 (Ser165) Antibody - #AF8080

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製品: Phospho-TGFBR1 (Ser165) Antibody
カタログ: AF8080
タンパク質の説明: Rabbit polyclonal antibody to Phospho-TGFBR1 (Ser165)
アプリケーション: WB
反応性: Human, Mouse, Rat
予測: Pig, Bovine, Sheep, Rabbit, Dog, Xenopus
分子量: 56 kDa.; 56kD(Calculated).
ユニプロット: P36897
RRID: AB_2840143

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MS Report
HPLC Report
MSDS
説明書
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WB Handbook
IHC Protocol
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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:1000-3000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Rat
予測:
Pig(100%), Bovine(100%), Sheep(100%), Rabbit(100%), Dog(100%), Xenopus(100%)
クローナリティ:
Polyclonal
特異性:
Phospho-TGFBR1 (Ser165) Antibody detects endogenous levels of TGFBR1 only when phosphorylated at TSer165.
RRID:
AB_2840143
引用形式: Affinity Biosciences Cat# AF8080, RRID:AB_2840143.
コンジュゲート:
Unconjugated.
精製:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ／展開

AAT 5; AAT5; Activin A receptor type II like kinase 53kDa; Activin A receptor type II like kinase, 53kD; Activin A receptor type II like protein kinase of 53kD; activin A receptor type II-like kinase, 53kDa; activin A receptor type II-like protein kinase of 53kD; Activin receptor like kinase 5; Activin receptor-like kinase 5; ACVRLK 4; ACVRLK4; ALK 5; ALK-5; ALK5; LDS1A; LDS2A; MSSE; Serine/threonine protein kinase receptor R4; Serine/threonine-protein kinase receptor R4; SKR 4; SKR4; TbetaR I; TbetaR-I; TGF beta receptor type 1; TGF beta receptor type I; TGF beta type I receptor; TGF-beta receptor type I; TGF-beta receptor type-1; TGF-beta type I receptor; TGFBR 1; TGFBR1; TGFBR1 protein; TGFR 1; TGFR-1; TGFR1; TGFR1_HUMAN; Transforming growth factor beta receptor 1; Transforming growth factor beta receptor I (activin A receptor type II like kinase, 53kD); Transforming growth factor beta receptor I; transforming growth factor, beta receptor 1; transforming growth factor, beta receptor I (activin A receptor type II-like kinase, 53kD); Transforming growth factor-beta receptor type I;

免疫原

免疫原:
Uniprot:

P36897(TGFR1_HUMAN) >>Visit HPA database.

遺伝子(ID):
TGFBR1(7046)
発現特異性:
P36897 TGFR1_HUMAN:

Found in all tissues examined, most abundant in placenta and least abundant in brain and heart. Expressed in a variety of cancer cell lines (PubMed:25893292).

タンパク質配列:
MEAAVAAPRPRLLLLVLAAAAAAAAALLPGATALQCFCHLCTKDNFTCVTDGLCFVSVTETTDKVIHNSMCIAEIDLIPRDRPFVCAPSSKTGSVTTTYCCNQDHCNKIELPTTVKSSPGLGPVELAAVIAGPVCFVCISLMLMVYICHNRTVIHHRVPNEEDPSLDRPFISEGTTLKDLIYDMTTSGSGSGLPLLVQRTIARTIVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSTASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDSINMKHFESFKRADIYAMGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSVEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLSQQEGIKM

種類予測

種類予測:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
100
Bovine
100
Sheep
100
Dog
100
Xenopus
100
Rabbit
100
Horse
0
Zebrafish
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P36897 基板として

Site PTM Type Enzyme
Ubiquitination
S165 Phosphorylation P37173 (TGFBR2)
S172 Phosphorylation P37173 (TGFBR2)
T176 Phosphorylation P37173 (TGFBR2)
K178 Ubiquitination
T185 Phosphorylation P37173 (TGFBR2)
T186 Phosphorylation P37173 (TGFBR2)
S187 Phosphorylation P37173 (TGFBR2)
S189 Phosphorylation P37173 (TGFBR2)
S191 Phosphorylation P37173 (TGFBR2)
T200 Phosphorylation P17252 (PRKCA)
T204 Phosphorylation
S210 Phosphorylation
T298 Phosphorylation
K337 Ubiquitination
K391 Ubiquitination
K449 Ubiquitination
K490 Ubiquitination
K502 Ubiquitination

PTMs - P36897 酵素として

Substrate Site Source
P17813 (ENG) S646 Uniprot
P17813 (ENG) S649 Uniprot
P68104 (EEF1A1) S300 Uniprot
P84022 (SMAD3) S422 Uniprot
P84022 (SMAD3) S423 Uniprot
P84022 (SMAD3) S425 Uniprot
Q03167 (TGFBR3) S831 Uniprot
Q15796 (SMAD2) S464 Uniprot
Q15796 (SMAD2) S465 Uniprot
Q15796 (SMAD2) S467 Uniprot
Q15797-1 (SMAD1) S462 Uniprot
Q15797-1 (SMAD1) S463 Uniprot
Q15797-1 (SMAD1) S465 Uniprot
Q96FW1 (OTUB1) S18 Uniprot
Q9H3D4-2 (TP63) S66 Uniprot
Q9H3D4 (TP63) S68 Uniprot
Q9H3D4 (TP63) S160 Uniprot

研究背景

機能:

Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.

PTMs:

Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding.

N-Glycosylated.

Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal. Its ubiquitination and proteasome-mediated degradation is negatively regulated by SDCBP.

細胞の位置付け:

Cell membrane>Single-pass type I membrane protein. Cell junction>Tight junction. Cell surface. Membrane raft.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Found in all tissues examined, most abundant in placenta and least abundant in brain and heart. Expressed in a variety of cancer cell lines.

サブユニット構造:

Homodimer; in the endoplasmic reticulum but also at the cell membrane. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGBRB1 and TGFBR2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Interacts with CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with SMAD7, NEDD4L, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor. Interacts with USP15 and VPS39. Interacts with SDCBP (via C-terminus) Interacts with CAV1 and this interaction is impaired in the presence of SDCBP. Interacts with APPL1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner.

タンパク質ファミリー:

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

研究領域

· Cellular Processes > Transport and catabolism > Endocytosis.   (View pathway)

· Cellular Processes > Cell growth and death > Cellular senescence.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Adherens junction.   (View pathway)

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signaling molecules and interaction > Cytokine-cytokine receptor interaction.   (View pathway)

· Environmental Information Processing > Signal transduction > FoxO signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > TGF-beta signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Apelin signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Hippo signaling pathway.   (View pathway)

· Human Diseases > Infectious diseases: Parasitic > Chagas disease (American trypanosomiasis).

· Human Diseases > Infectious diseases: Viral > Hepatitis B.

· Human Diseases > Infectious diseases: Viral > HTLV-I infection.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Colorectal cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Pancreatic cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Chronic myeloid leukemia.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

· Organismal Systems > Development > Osteoclast differentiation.   (View pathway)

· Organismal Systems > Immune system > Th17 cell differentiation.   (View pathway)

· Organismal Systems > Endocrine system > Relaxin signaling pathway.

参考文献

1). Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway. International Journal of Biological Sciences, 2023 (PubMed: 37781043) [IF=9.2]

Application: WB    Species: Mouse    Sample: OS cells

Figure 2 BEA inhibits the TGF-β/Smad2/3 signaling pathway in OS cells. (A) KEGG pathway enrichment analysis in BEA-treated and untreated 143B cells. (B) The effect of BEA on the TGF-β1-induced phosphorylation of Smad2/3, TGFBR1, and TGFBR2 in OS cells was evaluated by Western blotting. (C) Cellular immunofluorescence assay was performed to assess the nuclear translocation of p-Smad2/3 in OS cells treated with BEA. Scale bar: 20 μm. (D) The transcriptional activity of Smad2/3 in OS cells treated as indicated was determined by a Smad2/3 luciferase reporter assay. (E) 143B and U2OS cells were treated with BEA (2 μM) for 24 h and total RNA was harvested and analyzed by qPCR. Quantification of the mRNA levels of COL1A1, COL3A1, COL6A1, COL10A1, MMP2, LOX, LOXL2 in OS cells.
2). Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1. Phytomedicine, 2023 (PubMed: 37801895) [IF=7.9]
3). Caffeic acid mitigates myocardial fibrosis and improves heart function in post-myocardial infarction by inhibiting transforming growth factor-β receptor 1 signaling pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2024 (PubMed: 38906025) [IF=7.5]
4). 20(S)-ginsenoside Rg3 exerts anti-fibrotic effect after myocardial infarction by alleviation of fibroblasts proliferation and collagen deposition through TGFBR1 signaling pathways. Journal of Ginseng Research, 2023 [IF=6.3]

Application: WB    Species: Mouse    Sample: CFs

Fig. 6. TGFBR1 overexpression partly abolishes Rg3's inhibition on CFs growth, collagen synthesis, together with Smads activation. (A) CFs were infected with recombinant adenovirus for 48 h, and later stimulated by TGF-β1 (10 ng/ml) and Rg3 (20 μM), and Edu assay was performed to detect CFs proliferation (magnification, 200 × ). Red and blue fluorescence indicate proliferating cells as well as nuclei, separately. (B) Edu-positive cell proportion. (C) Expression of proliferation and collagen-related proteins in CFs following Ad-TGFBR1 or control adenovirus transfection. (D) Protein expression of TGFBR1 signaling in CFs after transfection. Relative PCNA (E), CDK6 (F), Cyclin D1 (G), collagen I (H), collagen III (I), p-TGFBR1 (J), p-Smad2 (K), and p-Smad3 (L) expression. Data are represented by mean ± SD for at least 3 groups. ∗p < 0.05, ∗∗p < 0.01. n.s, not significant.
5). Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization. Frontiers in Pharmacology, 2021 (PubMed: 33995055) [IF=5.6]

Application: WB    Species: mouse    Sample:

FIGURE 6 | BEL limits the expression of TβRI and the phosphorylation of TβRI and II induced by ISO (A and B) Western blotting analysis of TβRII, P-TβRII, TβRI, and P-TβRI. Bar graphs show fold changes of P-TβRI/GAPDH, TβRI/GAPDH and P-TβRII/TβRII (n 3).

Application: WB    Species: mouse    Sample: CFs

FIGURE 5 | BEL suppresses the TβR phosphorylation induced by TGF-β1 in CFs (A and B) Western blotting detects TβRⅠ and TβRⅡ expression and phosphorylation level. Bar graphs show fold changes for the ratio of phosphorylated (P)-TβRI/TβRI, and P-TβRⅡ/TβRⅡ as analyzed by western blotting. GAPDH was used as a loading control (n 3). Data were shown as mean ± SEM. **p < 0.01 vs. control, #
6). The aqueous extract of Gentianella acuta improves isoproterenol‑induced myocardial fibrosis via inhibition of the TGF‑β1/Smads signaling pathway. International Journal of Molecular Medicine, 2020 (PubMed: 31939619) [IF=5.4]

Application: WB    Species: rat    Sample: heart

Figure 5. | G. acuta causes a reduction in ISO-induced TβRI levels and the phosphorylation of TβRI and II. (A) Western blotting analysis of TβRII, phosphorylated (P)-TβRII, TβRI, P-TβRI.
7). Taohong siwu decoction attenuates myocardial fibrosis by inhibiting fibrosis proliferation and collagen deposition via TGFBR1 signaling pathway. Journal of Ethnopharmacology, 2021 (PubMed: 33460756) [IF=5.4]

Application: WB    Species: mice    Sample: cardiac fibroblasts

Fig. 6. THSWD suppresses expression of collagen and activation of the TGFBR1 signaling pathway. (A, B) CFs were incubated without or with TGF-β1 (10 ng/ml) and THSWD (15, 30 and 60 μg/ml) for 24 h, and the expression levels of collagen I, collagen III, collagen V, phospho-TGFBR1, TGFBR1, phospho-Smad2, Smad2, phospho-Smad3 and Smad3 were tested by western blotting. (C–E) Expression levels of collagen I, collagen III and collagen V were normalized with GAPDH (n = 3). (F–H) Expression levels of phospho-TGFBR1, phospho-Smad2, and phospho-Smad3 were normalized to that of TGFBR1, Smad2 and Smad3 proteins, respectively (n = 3). Data were shown as mean ± SD. #P < 0.05, vs. control group. *P < 0.05, **P < 0.01, vs. model group.
8). Pirfenidone alleviates cardiac fibrosis induced by pressure overload via inhibiting TGF‐β1/Smad3 signalling pathway. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2022 (PubMed: 35861038) [IF=5.3]

Application: WB    Species: Mouse    Sample: heart and primary cardiac fibroblasts

FIGURE 4Pirfenidone regulated the TGF-β1/Smad3 signalling pathway. (A–D) Western blotting and relative expression of TGF-β1 in mouse heart (n = 5–6) and primary cardiac fibroblasts (CFs) (n = 4), respectively. (E–H) Western blotting and relative expression of p-Smad3, Smad3 in mouse heart (n = 5–6) and CFs (n = 4), respectively. (I–L) Western blotting and relative expression of Smad7 in mouse heart (n = 5–6) and CFs (n = 4), respectively. *p < 0.05, **p < 0.01 vs. Sham/Ctrl group; #p < 0.05, ##p < 0.01 vs. TAC/AngII group
9). Riboflavin protects against pancreatic cancer metastasis by targeting TGF-β receptor 1. Bioorganic chemistry, 2024 (PubMed: 38503026) [IF=5.1]
10). TIPE2 suppresses malignancy of pancreatic cancer through inhibiting TGFβ1 mediated signaling pathway. Frontiers in Oncology, 2021 (PubMed: 34249724) [IF=4.7]

Application: WB    Species: Human    Sample: AsPC-1/vector and AsPC-1/TIPE2 cells

Figure 5 TIPE2 inhibited PI3K/AKT and Raf/MEK/ERK signaling pathways triggered by TGFβ1. (A) The total proteins extracted from cells were analyzed for the expression of AKT, ERK and Bax using western blot. The antibodies used were anti-pAKT, anti-AKT, anti-pERK, anti-ERK, anti-Bax and anti-GAPDH. (B) ELISA analysis of TGFβ1 secretion from AsPC-1/vector and AsPC-1/TIPE2 cells. (C) Immunohistochemistry analysis of the TGFβ1 expression in AsPC-1/vector and AsPC-1/TIPE2 tumor tissues. (D) Western blot analysis of the expression of p-TGFBR1 and total TGFBR1 in AsPC-1/vector and AsPC-1/TIPE2 cells. (E) AsPC-1 cells were seeded in 6-well plate and added with or without anti-TGFβ1 antibody or rhTGFβ1 protein. After 48 h incubation, the total proteins extracted from the cultured AsPC-1 cells were analyzed for the expression of AKT and ERK using western blot. The antibodies used were anti-pAKT, anti-AKT, anti-pERK, anti-ERK and anti-GAPDH. Data shown were representative of three independent experiments. Values are presented as means ± SD. ***p < 0.001.

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