Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''VCAM1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
VCAM-1 functions as a
cell adhesion molecule
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
.
Structure
VCAM-1 is a member of the
immunoglobulin superfamily
The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily ...
, the superfamily of proteins including
antibodies
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
and
T-cell receptors. The VCAM-1 gene contains six or seven
immunoglobulin
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
domains, and is expressed on both large and small
blood vessel
Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...
s only after the
endothelial
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...
cells are stimulated by
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s. It is
alternatively spliced
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
into two known
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
transcripts that encode different isoforms in humans. The gene product is a cell surface
sialoglycoprotein, a type I membrane protein that is a member of the
Ig superfamily.
Function
The VCAM-1 protein mediates the adhesion of
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...
s,
monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s,
eosinophil
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...
s, and
basophil
Basophils are a type of white blood cell
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and f ...
s to vascular
endothelium
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...
. It also functions in leukocyte-endothelial cell
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...
, and it may play a role in the development of
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
and
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
.
Upregulation of VCAM-1 in endothelial cells by cytokines occurs as a result of increased
gene transcription (e.g., in response to
tumor necrosis factor-alpha
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
(TNF-α) and
interleukin-1
The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Discovery
Discovery of these cytokines began with studies on t ...
(IL-1)) and through stabilization of
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
(mRNA) (e.g.,
Interleukin-4 (IL-4)). The promoter region of the ''VCAM1'' gene contains functional tandem
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...
(nuclear factor-kappa B) sites. The sustained expression of VCAM-1 lasts over 24 hours.
Primarily, the VCAM-1 protein is an endothelial
ligand
In coordination chemistry, a ligand is an ion or molecule with a 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 el ...
for
VLA-4 (Very Late Antigen-4 or integrin α4β1) of the β1 subfamily of
integrin
Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
s. VCAM-1 expression has also been observed in other cell types (e.g.,
smooth muscle cells
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal muscle, skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non-striated ...
). It has also been shown to
interact with
EZR and
Moesin
Moesin is a protein that in humans is encoded by the ''MSN'' gene.
Moesin (for membrane-organizing extension spike protein) is a member of the ERM protein family which includes ezrin and radixin. ERM proteins appear to function as cross-linkers ...
.
[
VCAM-1 is also upregulated if vWF (Von Willebrand Factor) is given in knock-out (KO) ADMATS13 mice but not on mice without KO.
CD106 also exists on the surface of some subpopulations of ]mesenchymal stem cell
Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can Cellular differentiation, differentiate into a variety of cell types, including osteoblasts (bone cells), ...
s (MSC).
Pharmacology
Certain melanoma
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
cells can use VCAM-1 to adhere to the endothelium, VCAM-1 may participate in monocyte recruitment to atherosclerotic sites, and it is highly overexpressed in the inflamed brain.drug
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
target.
References
Further reading
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External links
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{{Cell adhesion molecules
SIGLEC