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 as ...
and modulate signals for
transforming growth factor beta
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
ligands. These receptors are involved in a host of
physiological
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
processes including,
growth
Growth may refer to:
Biology
* Auxology, the study of all aspects of human physical growth
* Bacterial growth
* Cell growth
* Growth hormone, a peptide hormone that stimulates growth
* Human development (biology)
* Plant growth
* Secondary growth ...
,
cell differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellula ...
,
homeostasis
In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
,
osteogenesis
Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function ...
,
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
and many other functions. There are two activin type two receptors:
ACVR2A
Activin receptor type-2A is a protein that in humans is encoded by the ''ACVR2A'' gene.
ACVR2A is an activin type 2 receptor.
Function
This gene encodes activin A type II receptor. Activins are dimeric growth and differentiation factors which ...
and
ACVR2B
Activin receptor type-2B is a protein that in humans is encoded by the ''ACVR2B'' gene. ACVR2B is an activin type 2 receptor.
Function
Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-be ...
.
Despite the large amount of processes that these ligands regulate, they all operate through essentially the same pathway: A ligand binds to a type 2 receptor, which recruits and trans-
phosphorylate
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
s 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
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
.
Function
Several
ligands
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
that signal through the activin type 2 receptors regulate
muscle growth
Muscle hypertrophy or muscle building involves a hypertrophy or increase in size of skeletal muscle through a growth in size of its component cells. Two factors contribute to hypertrophy: sarcoplasmic hypertrophy, which focuses more on increased ...
.
Myostatin
Myostatin (also known as growth differentiation factor 8, abbreviated GDF8) is a protein that in humans is encoded by the ''MSTN'' gene. Myostatin is a myokine that is produced and released by myocytes and acts on muscle cells to inhibit muscle ...
, 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 may refer to:
Science, technology, and mathematics Computing
*Null (SQL) (or NULL), a special marker and keyword in SQL indicating that something has no value
*Null character, the zero-valued ASCII character, also designated by , often used ...
)
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s there was an increase in all four muscle groups studied ( pectoralis,
triceps
The triceps, or triceps brachii (Latin for "three-headed muscle of the arm"), is a large muscle on the back of the upper limb of many vertebrates. It consists of 3 parts: the medial, lateral, and long head. It is the muscle principally responsibl ...
,
quadriceps
The quadriceps femoris muscle (, also called the quadriceps extensor, quadriceps or quads) is a large muscle group that includes the four prevailing muscles on the front of the thigh. It is the sole extensor muscle of the knee, forming a large ...
, and
gastrocnemious
The gastrocnemius muscle (plural ''gastrocnemii'') is a superficial two-headed muscle that is in the back part of the lower leg of humans. It runs from its two heads just above the knee to the heel, a three joint muscle (knee, ankle and subtalar ...
/
plantaris
The plantaris is one of the superficial muscles of the superficial posterior compartment of the leg, one of the fascial compartments of the leg.
It is composed of a thin muscle belly and a long thin tendon. While not as thick as the achilles te ...
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 Gonocytes are the precursors of spermatogonia that differentiate in the testis from primordial germ cells around week 7 of embryonic development and exist up until the postnatal period, when they become spermatogonia. Despite some uses of the term t ...
as well as in
sertoli cells
Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimula ...
. These cells are responsive to both autocrine and paracrine activin B signaling, which controls their proliferation. Cells of the
epididymis
The epididymis (; plural: epididymides or ) is a tube that connects a testicle to a vas deferens in the male reproductive system. It is a single, narrow, tightly-coiled tube in adult humans, in length. It serves as an interconnection between the ...
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 cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
and tumors with
microsatellite
A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. ...
instability.
In a 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 (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
s the ACVR2A gene has been found mutated. It also plays a role in non-MSI-H colorectal cancers.
MDA
MDA, mda, or ''variation'', may refer to:
Places
* Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics
* Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...