Discoidin domain-containing receptor 2, also known as CD167b (
cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...
167b), is a protein that in humans is encoded by the DDR2
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 ...
.
Discoidin domain-containing receptor 2 is a
receptor tyrosine kinase
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinas ...
(RTK).
Function
RTKs play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation, and metabolism. In several cases the biochemical mechanism by which RTKs
transduce signals across the membrane has been shown to be ligand induced receptor oligomerization and subsequent intracellular
phosphorylation
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
. In the case of DDR2, the ligand is
collagen
Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
which binds to its extracellular discoidin domain.
This
autophosphorylation leads to phosphorylation of cytosolic targets as well as association with other molecules, which are involved in
pleiotropic effects of signal transduction. DDR2 has been associated with a number of diseases including
fibrosis and
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
.
Structure
RTKs have a tripartite structure with extracellular, transmembrane, and cytoplasmic regions. This gene encodes a member of a novel subclass of RTKs and contains a distinct extracellular region encompassing a
factor VIII
Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by ''F8'' gene. Defects in this gene result in hemophilia A, an X-linked bleeding disorder ...
-like domain.
Gene
Alternative splicing in the 5' UTR of the DDR2 gene results in multiple transcript variants encoding the same protein.
Interactions
DDR2 (gene) has been shown to
interact with
SHC1 and phosphorylate
Shp2.
DDR2 also interacts with
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 ...
α
1β
1 and α
2β
1 by promoting their adhesion to collagen.
References
Further reading
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Clusters of differentiation
Tyrosine kinase receptors