CD44
Encyclopedia
The CD44 antigen is a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

-surface glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the CD44 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...

.

Tissue distribution and isoforms

CD44 is expressed in a large number of mammalian cell types. The standard isoform
Protein isoform
A protein isoform is any of several different forms of the same protein. Different forms of a protein may be produced from related genes, or may arise from the same gene by alternative splicing. A large number of isoforms are caused by single-nucleotide polymorphisms or SNPs, small genetic...

, designated CD44s, comprising exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

s 1–5 and 16–20 is expressed in most cell types. CD44 splice variants containing variable exons are designated CD44v. Some epithelial cells
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 also express a larger isoform (CD44E), which includes exons v8–10.

Function

CD44 is a receptor for hyaluronic acid and can also interact with other ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

s, such as osteopontin
Osteopontin
Osteopontin , also known as bone sialoprotein I , early T-lymphocyte activation , secreted phosphoprotein 1 , 2ar and Rickettsia resistance , is a human gene product, which is also conserved in other species...

, collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...

s, and matrix metalloproteinase
Matrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....

s (MMPs). CD44 function is controlled by its posttranslational modifications. One critical modification involves discrete sialofucosylations rendering the selectin-binding glycoform of CD44 called HCELL (for Hematopoietic Cell E-selectin/L-selectin Ligand). The HCELL glycoform was originally discovered on human hematopoietic stem cells and leukemic blasts, and was subsequently identified on cancer cells. HCELL functions as a "bone homing receptor", directing migration of human hematopoietic stem cells and mesenchymal stem cells to bone marrow. Ex vivo glycan engineering of the surface of live cells has been used to enforce HCELL expression on any cell that expresses CD44. CD44 glycosylation also directly controls its binding capacity to fibrin and immobilized fibrinogen.

This protein participates in a wide variety of cellular functions including lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

 activation, recirculation and homing, hematopoiesis, and tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. Transcripts for this 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...

 undergo complex alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. Splice variants of CD44 on colon cancer cells display sialofucosylated HCELL glycoforms that serve as P-, L-, and E-selectin ligands and fibrin, but not fibrinogen, receptors under hemodynamic flow conditions pertinent to the process of cancer metastasis. CD44 gene transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

 is at least in part activated by beta-catenin
Beta-catenin
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...

 and Wnt signalling
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...

 (also linked to tumour development).

Clinical significance

The protein is a determinant for the Indian blood group system
Indian blood group system
The Indian blood group system is named because 4% of the population in India possess it . It is a classification of blood based on the presence or absence of inherited antigens that reside within the CD44 molecule that is expressed on the surface of blood cells. Most individuals express the Inb...

.
  • CD44, along with CD25
    CD25
    CD25 is the alpha chain of the IL-2 receptor. It is a type I transmembrane protein present on activated T cells, activated B cells, some thymocytes, myeloid precursors, and oligodendrocytes that associates with CD122 to form a heterodimer that can act as a high-affinity receptor for IL-2.CD25 is...

    , is used to track early T cell
    T 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...

     development in the thymus
    Thymus
    The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....

    .

  • CD44 expression is an indicative marker for effector-memory T-cells. Memory cell proliferation (activation) can also be assayed in vitro with CFSE chemical tagging.


In addition, variations in CD44 are reported as cell surface markers for some breast and prostate cancer stem cells. and has been seen as an indicator of increased survival time in epithelial ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....

 patients.

Endometrial cells in women with endometriosis
Endometriosis
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...

 demonstrate increased expression of splice variants of CD44, and increased adherence to peritoneal cells.

CD44 variant isoforms are also relevant to the progression of head and neck squamous cell carcinoma
Head and neck cancer
Head and neck cancer refers to a group of biologically similar cancers that start in the upper aerodigestive tract, including the lip, oral cavity , nasal cavity , paranasal sinuses, pharynx, and larynx. 90% of head and neck cancers are squamous cell carcinomas , originating from the mucosal lining...

.

Monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....

 against CD44 variants include bivatuzumab
Bivatuzumab
Bivatuzumab is a humanized monoclonal antibody against CD44 v6.It is officially described as "immunoglobulin G1 , disulfide with human-mouse monoclonal BIWA4 κ-chain, dimer"...

 for v6.

Interactions

CD44 has been shown to interact
Protein-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:
  • ARHGEF1
    ARHGEF1
    Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene.-Interactions:ARHGEF1 has been shown to interact with GNA13, CD44, P110α and GNA12.-Further reading:...

    ,
  • fibrin
    Fibrin
    Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....

     and immobilized fibrinogen
    Fibrinogen
    Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...

    .
  • Fibronectin
    Fibronectin
    Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...

    ,
  • FYN
    FYN
    Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...

    ,
  • Lck
    Lck
    Lck is a protein that is found inside specialized cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes...

    ,
  • selectins, and
  • Src
    Src (gene)
    Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...

    .

External links

  • Indian blood group system at BGMUT
    BGMUT
    The BGMUT Database documents allelic variations in the genes encoding for human blood group systems. It was set up in 1999 through an initiative of the Human Genome Variation Society . Since 2006, it has been a part of the dbRBC resource of NCBI at the NIH...

     Blood Group Antigen Gene Mutation Database at NCBI
    National Center for Biotechnology Information
    The National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...

    , NIH
  • Articles at IHOP
    Information Hyperlinked over Proteins
    Information Hyperlinked over Proteins is an online service that provides a gene-guided network to access PubMed abstracts. By using genes and proteins as hyperlinks between sentences and abstracts, the information in PubMed can be converted into one navigable resource.Navigating across...

    .
The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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