Transforming growth factor beta receptor I (activin A receptor type II-like kinase, 53kDa) is a membrane-bound
TGF beta receptor
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. (free full text) The number ...
protein of the
TGF-beta receptor family
The transforming growth factor beta (TGFβ) receptors are a family of serine/threonine kinase receptors involved in TGF beta signaling pathway. These receptors bind growth factor and cytokine signaling proteins in the TGF-beta family such ...
for the
TGF beta superfamily of signaling ligands. ''TGFBR1'' is its human
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
The protein encoded by this gene forms a heteromeric complex with
type II TGF-β receptors when bound to TGF-β, transducing the TGF-β signal from the cell surface to the cytoplasm. The encoded protein is a
serine/threonine protein kinase
A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human prote ...
. Mutations in this gene have been associated with
Loeys–Dietz aortic aneurysm syndrome (LDS, LDAS).
Interactions
TGF beta receptor 1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...
with:
*
Caveolin 1
Caveolin-1 is a protein that in humans is encoded by the ''CAV1'' gene.
Function
The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits ...
,
*
Endoglin
Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefor ...
,
*
FKBP1A
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' gene.
Function
The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basi ...
,
*
FNTA
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha is an enzyme that in humans is encoded by the ''FNTA'' gene.
Prenyltransferases attach either a farnesyl group or a geranylgeranyl group in thioether linkage to the cyst ...
,
*
Heat shock protein 90kDa alpha (cytosolic), member A1
Heat shock protein HSP 90-alpha is a protein that in humans is encoded by the ''HSP90AA1'' gene.
Function
The gene, HSP90AA1, encodes the human stress-inducible 90-kDa heat shock protein alpha (Hsp90A). Complemented by the constitutively ex ...
*
Mothers against decapentaplegic homolog 7
Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the ''SMAD7'' gene.
SMAD7 is a protein that, as its name describes, is a homolog of the Drosophila gene: "Mothers against decapentaplegic". It belongs to ...
,
*
PPP2R2A
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform is an enzyme regulator that in humans is encoded by the ''PPP2R2A'' gene.
Function
The product of this gene belongs to the phosphatase 2 regulatory subunit B fam ...
,
*
STRAP
A strap, sometimes also called strop, is an elongated flap or ribbon, usually of leather or other flexible materials.
Thin straps are used as part of clothing or baggage, or bedding such as a sleeping bag. See for example spaghetti strap, ...
,
* TGF beta 1
TGF may refer to:
Medicine
* Tubuloglomerular feedback, a reflex of the nephrons in the kidney
* Transforming growth factor, either of two classes of polypeptide growth factors (TGF-α and TGF-β)
Science
* Terrestrial gamma-ray flash, a burst ...
, and
* TGF beta receptor 2
Transforming growth factor, beta receptor II (70/80kDa) is a TGF beta receptor. ''TGFBR2'' is its human gene.
It is a tumor suppressor gene.
Function
This gene encodes a member of the serine/threonine protein kinase family and the TGFB recepto ...
.
Inhibitors
* GW-788,388
* LY-2109761
* Galunisertib
Galunisertib (LY2157299) is a small molecular experimental cancer drug previously in development by Eli Lilly. It is a TGF-b inhibitor. Development of galunisertib by Eli Lilly was discontinued in January 2020.
Galunisertib was investigated in a ...
(LY-2157299)
* SB-431,542
* SB-525,334
* Repsox
Animal studies
Defects are observed when the TGFBR-1 gene is either knocked-out or when a constitutively active TGFBR-1 mutant (that is active in the presence or absence of ligand) is knocked-in.
In mouse TGFBR-1 knock-out models, the female mice were sterile. They developed oviductal diverticula and defective uterine smooth muscle, meaning that uterine smooth muscle layers were poorly formed. Oviductal diverticula are small, bulging pouches located on the oviduct
The oviduct in mammals, is the passageway from an ovary. In human females this is more usually known as the Fallopian tube or uterine tube. The eggs travel along the oviduct. These eggs will either be fertilized by spermatozoa to become a zygote, ...
, which is the tube that transports the ovum from the ovary to the uterus. This deformity of the oviduct occurred bilaterally and resulted in impaired embryo development and impaired transit of the embryos to the uterus. Ovulation and fertilization still occurred in the knock-outs, however remnants of embryos were found in these oviductal diverticula.
In mouse TGFBR-1 knock-in models where a constitutively active TGFBR-1 gene is conditionally induced, the over-activation of the TGFBR-1 receptors lead to infertility, a reduction in the number of uterine glands, and hypermuscled uteri (an increased amount of smooth muscle in the uteri).
These experiments show that the TGFB-1 receptor plays a critical role in the function of the female reproductive tract. They also show that genetic mutations in the TGFBR-1 gene may lead to fertility issues in women.
References
Further reading
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*
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External links
GeneReviews/NIH/NCBI/UW entry on Thoracic Aortic Aneurysms and Aortic Dissections
GeneReviews/NCBI/NIH/UW entry on Loeys-Dietz Syndrome
{{TGFβ receptor superfamily modulators
TGF beta receptors