TGF beta receptor - Misplaced Pages

Transforming growth factor beta (TGFβ) receptors are single pass serine/threonine kinase receptors that belong to TGFβ receptor family. They exist in several different isoforms that can be homo- or heterodimeric. The number of characterized ligands in the TGFβ superfamily far exceeds the number of known receptors, suggesting the promiscuity that exists between the ligand and receptor interactions.

TGFβ is a growth factor and cytokine involved in paracrine signalling and can be found in many different tissue types, including brain, heart, kidney, liver, bone, and testes. Over-expression of TGFβ can induce renal fibrosis, causing kidney disease, as well as diabetes, and ultimately end-stage renal disease. Recent developments have found that, using certain types of protein antagonists against TGFβ receptors, can halt and in some cases reverse the effects of renal fibrosis.

Three TGFβ superfamily receptors specific for TGFβ, the TGFβ receptors, can be distinguished by their structural and functional properties. TGFβR1 (ALK5) and TGFβR2 have similar ligand-binding affinities and can be distinguished from each other only by peptide mapping. Both TGFβR1 and TGFβR2 have a high affinity for TGFβ1 and low affinity for TGFβ2. TGFβR3 (β-glycan) has a high affinity for both homodimeric TGFβ1 and TGFβ2 and in addition the heterodimer TGF-β1.2. The TGFβ receptors also bind TGFβ3.

References

Doré JJ, Edens M, Garamszegi N, Leof EB (November 1998). "Heteromeric and homomeric transforming growth factor-beta receptors show distinct signaling and endocytic responses in epithelial cells". The Journal of Biological Chemistry. 273 (48): 31770–7. doi:10.1074/jbc.273.48.31770. PMID 9822641. (free full text)
Cheifetz S, Andres JL, Massagué J (November 1988). "The transforming growth factor-beta receptor type III is a membrane proteoglycan. Domain structure of the receptor". The Journal of Biological Chemistry. 263 (32): 16984–91. doi:10.1016/S0021-9258(18)37487-8. PMID 2903157.

External links

TGF-beta+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Cell signaling: TGFβ signaling pathway

TGF beta superfamily of ligands

Ligand of ACVR or TGFBR	TGF beta family TGF-β1 TGF-β2 TGF-β3 Activin and inhibin INHA INHBA INHBB INHBC Nodal
Ligand of BMPR	Bone morphogenetic proteins BMP2 BMP3 BMP4 BMP5 BMP6 BMP7 BMP8a BMP8b BMP10 BMP15 Growth differentiation factors GDF1 GDF2 GDF3 GDF5 GDF6 GDF7 Myostatin/GDF8 GDF9 GDF10 GDF11 GDF15 Anti-müllerian hormone

TGF beta receptors
(Activin, BMP, family)

TGFBR1:	Activin type 1 receptors ACVR1 ACVR1B ACVR1C ACVRL1 BMPR1 BMPR1A BMPR1B
TGFBR2:	Activin type 2 receptors ACVR2A ACVR2B AMHR2 BMPR2
TGFBR3:	betaglycan

Transducers/SMAD

Ligand inhibitors

Coreceptors

BAMBI
Cripto

Other

SARA

Receptors: growth factor receptors

Type I cytokine receptor

Receptor protein serine/threonine kinase

Receptor tyrosine kinase

Fibroblast growth factor 1 2 3 4
Nerve growth factors: high affinity Trk TrkA TrkB TrkC
Hepatocyte growth factor
Somatomedin Insulin-like growth factor 1
ErbB/Epidermal growth factor
VEGF 1 2 3

Tumor necrosis factor receptor

Nerve growth factors: Low affinity/p75

Ig superfamily

Other/ungrouped

Somatomedin
- Insulin-like growth factor 2

Cytokine receptors

Chemokine receptor
(GPCRs)

CC	CCR1 / CCRL1 CCR2 CCRL2 CCR3 CCR4 CCR5 CCR6 CCR7 CCR8 CCR9 CCR10
CXC	IL-8 CXCR1 CXCR2 CXCR3 CXCR4 CXCR5 CXCR6 CXCR7
Other	CX3C CX3CR1 XC XCR1 CCBP2 CMKLR1

TNF receptor

1-10	TNFR1 (TNFRSF1A) TNFR2 (TNFRSF1B) LTBR (TNFRSF3) CD134 (TNFRSF4) CD40 (TNFRSF5) Fas receptor (TNFRSF6) DcR3 (TNFRSF6B) CD27 (TNFRSF7) CD30 (TNFRSF8) CD137 (TNFRSF9)
11-20	DR4 (TNFRSF10A) DR5 (TNFRSF10B) DcR1 (TNFRSF10C) DcR2 (TNFRSF10D) RANK (TNFRSF11A) Osteoprotegerin (TNFRSF11B) TweakR (TNFRSF12A) TACI (TNFRSF13B) BAFFR (TNFRSF13C) HVEM (TNFRSF14) NGFR (TNFRSF16) BCMA (TNFRSF17) GITR (TNFRSF18) TAJ/TROY (TNFRSF19)
21-27	DR6 (TNFRSF21) DR3 (TNFRSF25) EDA2R (TNFRSF27)

JAK-STAT

Type I

γ-chain	Interleukin receptors IL2R / IL2RA/IL2RB / IL15R IL4R / IL13R / IL13RA1 / IL13RA2 IL7R / IL7RA IL9R IL21R
β-chain	Interleukin receptors IL3R / IL3RA IL5R / IL5RA GM-CSF
gp130	Interleukin receptors IL6RA 11/IL11RA 27/IL27RA OSMR LIFR CNTFR
IL12RB1	Interleukin receptors IL12R/IL12RB1/IL12RB2 IL23R
Other	other CSF receptors EPO G-CSF Thrombopoietin hormone receptor: GH prolactin

Type II

Interleukin receptors
- IL10R / IL10RA / IL10RB / IL22R / IL22RA1 / IL22RA2
- IL20R / IL20RA / IL20RB
- IL28R
Interferon receptors
- -α/β / IFNAR1/IFNAR2
- -γ/IFNGR1 / IFNGR2

Ig superfamily

IL1
- IL1R1
- IL1R2
IL18R / IL18R1

IL 17 family

IL17
- IL17RA
- IL17RB
- IL17RC
- IL17RD
- IL17RE

Enzyme-linked receptor

Tyr
- CSF1R
- KIT
Ser/Thr: TGF-beta
- TGFBR1
- TGFBR2
- family

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated mTOR EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1
Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3 PDK4
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4
Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase Aurora C kinase
Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-
IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP
cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY
cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1
Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3
Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase
Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2
G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6
Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK1A CAMK1B CAMK1D CAMK1G CAMK2 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1
Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4
Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2
Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19
Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4
Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1
Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14
MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14
Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3
(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-
Tropomyosin kinase (EC 2.7.11.28)	-
Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-
Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

TGFβ receptor superfamily modulators

Type I

ALK1 (ACVRL1)	Agonists: Activin (A, B, AB) Avotermin BMP (10) Cetermin GDF (2 (BMP9)) TGFβ (1, 2, 3) Antibodies: Ascrinvacumab Kinase inhibitors: K-02288 ML-347 (LDN-193719, VU0469381) Decoy receptors: Dalantercept Other inhibitors: Disitertide
ALK2 (ACVR1A)	Agonists: Activin (A, B, AB) AMH (MIS) Avotermin BMP (5, 6, 7, 8A, 8B) Eptotermin alfa TGFβ (1, 2, 3) Kinase inhibitors: DMH-1 DMH-2 Dorsomorphin (BML-275) K-02288 ML-347 (LDN-193719, VU0469381)
ALK3 (BMPR1A)	Agonists: AMH (MIS) BMP (2, 4, 5, 6, 7, 8A, 8B) Dibotermin alfa Eptotermin alfa Kinase inhibitors: DMH-2 Dorsomorphin (BML-275) K-02288
ALK4 (ACVR1B)	Agonists: Activin (A, B, AB) GDF (1, 3, 11 (BMP11)) Myostatin (GDF8) Nodal Antagonists: Inhibin (A, B) Lefty (1, 2) Kinase inhibitors: A 83-01 SB-431542 SB-505124
ALK5 (TGFβR1)	Agonists: Avotermin GDF (10 (BMP3B), 11 (BMP11)) TGFβ (1, 2, 3) Antibodies: Fresolimumab Lerdelimumab Metelimumab Kinase inhibitors: A 83-01 D-4476 GW-788388 LY-364947 LY-2109761 Galunisertib (LY-2157299) R-268712 RepSox (E-616452, SJN-2511) SB-431542 SB-505124 SB-525334 SD-208
ALK6 (BMPR1B)	Agonists: BMP (2, 4, 5, 6, 7, 8A, 8B, 15 (GDF9B)) Dibotermin alfa Eptotermin alfa GDF (5 (BMP14), 6 (BMP13), 7 (BMP12), 9, 15) Radotermin Kinase inhibitors: DMH-2 Dorsomorphin (BML-275) K-02288
ALK7 (ACVR1C)	Agonists: GDF (1, 3, 11 (BMP11)) Nodal Antagonists: Lefty (1, 2) Kinase inhibitors: A 83-01 SB-431542 SB-505124

Type II

TGFβR2	Agonists: Avotermin GDF (10 (BMP3B)) TGFβ (1, 2, 3) Antibodies: Fresolimumab Lerdelimumab Metelimumab Kinase inhibitors: DMH-2 LY-364947
BMPR2	Agonists: BMP (2, 4, 6, 7, 10) Dibotermin alfa Eptotermin alfa GDF (2 (BMP9), 5 (BMP14), 6 (BMP13), 7 (BMP12)) Radotermin Antagonists: Inhibin (A, B)
ACVR2A (ACVR2)	Agonists: Activin (A, B, AB) BMP (2, 4, 5, 6, 7, 8A, 8B, 15 (GDF9B)) Dibotermin alfa Eptotermin alfa GDF (1, 3, 5 (BMP14), 6 (BMP13), 7 (BMP12), 9, 11 (BMP11), 15) Myostatin (GDF8) Nodal Radotermin Antagonists: Inhibin (A, B) Lefty (1, 2) Decoy receptors: Sotatercept
ACVR2B	Agonists: Activin (A, B, AB) BMP (2, 4, 6, 7) Dibotermin alfa Eptotermin alfa GDF (1, 3, 5 (BMP14), 6 (BMP13), 7 (BMP12)) Myostatin (GDF8) Nodal Osteogenin (BMP3, BMP3A) Radotermin Antagonists: Inhibin (A, B) Lefty (1, 2) Decoy receptors: Ramatercept
AMHR2 (AMHR)	Agonists: AMH (MIS)

Type III

TGFβR3 (β-glycan)	Ligands: Avotermin Inhibin (A, B) TGFβ (1, 2, 3)

Unsorted

Endogenous antagonists/inhibitors: BAMBI
Cerberus (CER1)
Chordin
DAN (PARN)
Decorin
Follistatin
Gremlin (Drm)
LTBP1
Noggin
TGIF
Thrombospondin 1 (THBS1)
Tomoregulin 1

Antibodies: Stamulumab (against myostatin)
TRC105 (against endoglin)

Others: Endoglin

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References

External links