TGF beta 1
Encyclopedia
Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily
of cytokine
s. It is a secreted protein that performs many cellular functions, including the control of cell growth
, cell proliferation, cell differentiation and apoptosis
. In humans, TGF-β1 is encoded by the TGFB1 gene
.
, and other functions in many cell types. TGFB acts synergistically with TGFA in inducing transformation. It also acts as a negative autocrine growth factor
. Dysregulation of TGFB activation and signaling may result in apoptosis
. Many cells synthesize TGFB and almost all of them have specific receptors for this peptide. TGFB1, TGFB2, and TGFB3 all function through the same receptor signaling systems.[supplied by OMIM]
TGF-β1 was first identified in human platelet
s as a protein with a molecular mass of 25 kilodaltons with a potential role in wound healing
. It was later characterized as a large protein precursor
(containing 390 amino acid
s) that was proteolytically
processed to produce a mature peptide of 112 amino acids.
TGF-β1 plays an important role in controlling the immune system
, and shows different activities on different types of cell, or cells at different developmental stages. Most immune cells (or leukocytes) secrete TGF-β1.
s (e.g. regulatory T cell
s) release TGF-β1 to inhibit the actions of other T cells. Interleukin 1- and interleukin 2
-dependent proliferation of activated T cells, and the activation of quiescent helper T cells and cytotoxic T cell
s is prevented by the activity of TGF-β1. Similarly, TGF-β1 can inhibit the secretion and activity of many other cytokine
s including interferon-γ
, tumor necrosis factor-alpha (TNF-α) and various interleukin
s. It can also decrease the expression levels of cytokine receptors, such as the IL-2 receptor to down-regulate the activity of immune cells. However, TGF-β1 can also increase the expression of certain cytokines in T cells and promote their proliferation, particularly if the cells are immature.
s that also vary according to the differentiation state of the cell. It inhibits proliferation and stimulates apoptosis
of B cells, and plays a role in controlling the expression of antibody
, transferrin
and MHC class II
proteins on immature and mature B cells.
s and monocyte
s is predominantly suppressive; this cytokine can inhibit the proliferation of these cells and prevent their production of reactive oxygen (e.g. superoxide (O2−)) and nitrogen (e.g. nitric oxide (NO)) intermediates. However, as with other cell types, TGF-β1 can also have the opposite effect on cells of myeloid origin. For example, TGF-β1 acts as a chemoattractant, directing an immune response to some pathogen
s; macrophages and monocytes respond to low levels of TGF-β1 in a chemotactic manner. Furthermore, the expression of monocytic cytokines (including interleukin-1(IL-1)-alpha, IL-1-beta, and TNF-α), and phagocytic killing by macrophages can be increased by the action of TGF-β1.
with TGF beta receptor 1
, LTBP1
, YWHAE
, EIF3I
and Decorin
.
Transforming growth factor beta superfamily
The transforming growth factor beta superfamily is a large family of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983....
of cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s. It is a secreted protein that performs many cellular functions, including the control of cell 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 proliferation, cell differentiation and 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...
. In humans, TGF-β1 is encoded by the TGFB1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
TGFB is a multifunctional peptide that controls proliferation, differentiationCellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
, and other functions in many cell types. TGFB acts synergistically with TGFA in inducing transformation. It also acts as a negative autocrine growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
. Dysregulation of TGFB activation and signaling may result in 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...
. Many cells synthesize TGFB and almost all of them have specific receptors for this peptide. TGFB1, TGFB2, and TGFB3 all function through the same receptor signaling systems.[supplied by OMIM]
TGF-β1 was first identified in human platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s as a protein with a molecular mass of 25 kilodaltons with a potential role in wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
. It was later characterized as a large protein precursor
Protein precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein that can be turned into an active form by posttranslational modification. The name of the precursor for a protein is often prefixed by pro...
(containing 390 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s) that was proteolytically
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
processed to produce a mature peptide of 112 amino acids.
TGF-β1 plays an important role in controlling the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, and shows different activities on different types of cell, or cells at different developmental stages. Most immune cells (or leukocytes) secrete TGF-β1.
TGF-β1 and T cells
Some T cellT cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s (e.g. regulatory T cell
Regulatory T cell
Regulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...
s) release TGF-β1 to inhibit the actions of other T cells. Interleukin 1- and interleukin 2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
-dependent proliferation of activated T cells, and the activation of quiescent helper T cells and cytotoxic T cell
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
s is prevented by the activity of TGF-β1. Similarly, TGF-β1 can inhibit the secretion and activity of many other cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s including interferon-γ
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
, tumor necrosis factor-alpha (TNF-α) and various interleukin
Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...
s. It can also decrease the expression levels of cytokine receptors, such as the IL-2 receptor to down-regulate the activity of immune cells. However, TGF-β1 can also increase the expression of certain cytokines in T cells and promote their proliferation, particularly if the cells are immature.
TGF-β1 and B cells
TGF-β1 has similar effects on B cellB cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s that also vary according to the differentiation state of the cell. It inhibits proliferation and stimulates 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...
of B cells, and plays a role in controlling the expression of antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
and MHC class II
MHC class II
MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....
proteins on immature and mature B cells.
TGF-β1 and myeloid cells
The effects of TGF-β1 on macrophageMacrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s and monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s is predominantly suppressive; this cytokine can inhibit the proliferation of these cells and prevent their production of reactive oxygen (e.g. superoxide (O2−)) and nitrogen (e.g. nitric oxide (NO)) intermediates. However, as with other cell types, TGF-β1 can also have the opposite effect on cells of myeloid origin. For example, TGF-β1 acts as a chemoattractant, directing an immune response to some pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s; macrophages and monocytes respond to low levels of TGF-β1 in a chemotactic manner. Furthermore, the expression of monocytic cytokines (including interleukin-1(IL-1)-alpha, IL-1-beta, and TNF-α), and phagocytic killing by macrophages can be increased by the action of TGF-β1.
Interactions
TGF beta 1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with TGF beta receptor 1
TGF beta receptor 1
Transforming growth factor, beta receptor I is a TGF beta receptor. TGFBR1 is its human gene.-Interactions:...
, LTBP1
LTBP1 (gene)
Latent-transforming growth factor beta-binding protein 1 is a protein that in humans is encoded by the LTBP1 gene.-Interactions:LTBP1 has been shown to interact with TGF beta 1.-Further reading:...
, YWHAE
YWHAE
14-3-3 protein epsilon is a protein that in humans is encoded by the YWHAE gene.-Interactions:YWHAE has been shown to interact with CDC25B, Insulin-like growth factor 1 receptor, NGFRAP1, TGF beta 1, HERG, C-Raf, NDEL1, HDAC4, IRS1 and MAP3K3....
, EIF3I
EIF3I
Eukaryotic translation initiation factor 3 subunit I is a protein that in humans is encoded by the EIF3I gene.-Interactions:EIF3I has been shown to interact with TGF beta 1 and EIF3A.-Further reading:...
and Decorin
Decorin
Decorin is a proteoglycan on average 90 - 140 kilodaltons in size.It belongs to the small leucine-rich proteoglycan family and consists of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate .Decorin is a small...
.