The interleukin-3 receptor (
CD123) is a molecule found on cells which helps transmit the signal of
interleukin-3
Interleukin 3 (IL-3) is a protein that in humans is encoded by the ''IL3'' gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein ...
, a soluble
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
important in the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...
.
The
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
coding for the receptor is located in the
pseudoautosomal region
The pseudoautosomal regions, PAR1, PAR2, are homologous sequences of nucleotides on the X and Y chromosomes.
The pseudoautosomal regions get their name because any genes within them (so far at least 29 have been found for humans) are inherited j ...
of the
X and
Y chromosome
The Y chromosome is one of two sex chromosomes ( allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or a ...
s.
The receptor belongs to the
type I cytokine receptor
Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands. These receptors are also known under the name '' hemopoietin receptors'', and share a ...
family and is a
heterodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
with a unique alpha chain paired with the
common beta (beta c or CD131) subunit.
The gene for the alpha subunit is 40
kilobase
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both ...
s long and has 12
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequenc ...
s.
Cell types and function
The receptor, found on
pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
progenitor cells, induces
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
phosphorylation
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, ...
within the cell and promotes proliferation and differentiation within the
hematopoietic cell
A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), ...
lines. It can be found on
basophil
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammato ...
s and
pDC PDC may refer to:
In science and technology Chemistry, biology and medicine
* Phosducin, a human protein and gene in the retina
* Pyridinium dichromate (Cornforth reagent), a chromium-based oxidant
* Pyruvate dehydrogenase complex, an enzyme ...
s as well as some
cDC
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
s among peripheral blood mononuclear cells.
CD123 is expressed across
acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympto ...
(AML) subtypes, including leukemic
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...
s.
[ Seattle Genetics Initiates Phase 1 Trial of SGN-CD123A for Patients with Relapsed or Refractory Acute Myeloid Leukemia Sept 2016]
/ref>
Possible drug target
Tagraxofusp, human IL-3 fused to diphtheria toxin, is an approved treatment for BPDCN.
An experimental antibody-drug conjugate
Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 phar ...
SGN-CD123A targets CD123 as a possible treatment for AML.[
]
References
External links
*
{{Interleukin receptor modulators
Type I cytokine receptors