Activin type 2 receptors
Encyclopedia
The Activin type 2 receptors modulate signals for ligands belonging to the Transforming growth factor beta superfamily of ligands. These include: Activin (or Inhibin), Bone morphogenetic proteins and Nodal. They are involved in a host of physiological
processes including, growth
, cell differentiation, homeostasis
, osteogenesis, apoptosis
and many other functions. There are two Activin type two receptors: ACVR2A
and ACVR2B
.
Despite the large amount of processes that these ligands regulate, they all operate through essentially the same pathway
: A ligand binds to a Type two receptor, which recruits and trans-phosphorylates a type I receptor. The type I receptor recruits a receptor regulated SMAD (R-SMAD) which it phosphorylates. The RSMAD then translocates to the nucleus where it functions as a transcription factor
.
, a TGF-beta superfamily member, is a negative regulator of muscle growth. Myostatin binds to ACVR2B and to a lesser extent ACVR2A. In mice that were ACVR2A -/- (null
) mutant
s there was an increase in all four muscle groups studied (pectoralis, triceps, quadriceps, and gastrocnemious/plantaris muscles). Two of these muscle groups (pectoralis and triceps)were increased in ACVR2B -/- (null) mutants. Activin plays a significant role in reproduction. ACVR2 receptors are present in the testis during testicular development.
ACR2A and ACVR2B was found to be localized primarily in the gonocytes as well as in sertoli cells. These cells are responsive to both autocrine and paracrine Activin B signaling, which controls their proliferation. Cells of the epididymis
also have ACVR2A receptors present. ACVR2B receptors were found to be localized in the rete testis.
and tumors with microsatellite instability.
In the lab, it has been shown that truncated mutations in the ACVR2 gene causes a significant reduction in activin mediated cell signaling. In 58.1% of microsatellite unstable (MSI-H) colorectal cancer
s the ACVR2A gene has been found mutated. It also plays a role in non - MSI-H colorectal cancers.
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
processes including, growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
, cell differentiation, homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
, osteogenesis, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
and many other functions. There are two Activin type two receptors: ACVR2A
ACVR2A
Activin receptor type-2A is a protein that in humans is encoded by the ACVR2A gene.ACVR2A is an activin type 2 receptor.-Interactions:ACVR2A has been shown to interact with INHBA, SYNJ2BP and ACVR1B.-Further reading:...
and ACVR2B
ACVR2B
Activin receptor type-2B is a protein that in humans is encoded by the ACVR2B gene. ACVR2B is an activin type 2 receptor.-Interactions:ACVR2B has been shown to interact with SYNJ2BP and ACVR1B.-Further reading:...
.
Despite the large amount of processes that these ligands regulate, they all operate through essentially the same pathway
TGF beta signaling pathway
The Transforming growth factor beta signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. In spite of the wide range of cellular...
: A ligand binds to a Type two receptor, which recruits and trans-phosphorylates a type I receptor. The type I receptor recruits a receptor regulated SMAD (R-SMAD) which it phosphorylates. The RSMAD then translocates to the nucleus where it functions as a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
.
Function
Several ligands that signal through the Activin type II receptors regulate muscle growth. MyostatinMyostatin
Myostatin is a secreted TGF beta protein family member that inhibits muscle differentiation and growth. Myostatin is produced primarily in skeletal muscle cells, circulates in the blood and acts on muscle tissue, by binding a cell-bound receptor called the activin type II receptor...
, a TGF-beta superfamily member, is a negative regulator of muscle growth. Myostatin binds to ACVR2B and to a lesser extent ACVR2A. In mice that were ACVR2A -/- (null
Null allele
A null allele is a mutant copy of a gene that completely lacks that gene's normal function. This can be the result of the complete absence of the gene product at the molecular level, or the expression of a non-functional gene product...
) mutant
Mutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
s there was an increase in all four muscle groups studied (pectoralis, triceps, quadriceps, and gastrocnemious/plantaris muscles). Two of these muscle groups (pectoralis and triceps)were increased in ACVR2B -/- (null) mutants. Activin plays a significant role in reproduction. ACVR2 receptors are present in the testis during testicular development.
ACR2A and ACVR2B was found to be localized primarily in the gonocytes as well as in sertoli cells. These cells are responsive to both autocrine and paracrine Activin B signaling, which controls their proliferation. Cells of the epididymis
Epididymis
The epididymis is part of the male reproductive system and is present in all male amniotes. It is a narrow, tightly-coiled tube connecting the efferent ducts from the rear of each testicle to its vas deferens. A similar, but probably non-homologous, structure is found in cartilaginous...
also have ACVR2A receptors present. ACVR2B receptors were found to be localized in the rete testis.
Clinical significance
The ACVR2 gene is often found inactivated in prostate cancerProstate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
and tumors with microsatellite instability.
In the lab, it has been shown that truncated mutations in the ACVR2 gene causes a significant reduction in activin mediated cell signaling. In 58.1% of microsatellite unstable (MSI-H) colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
s the ACVR2A gene has been found mutated. It also plays a role in non - MSI-H colorectal cancers.