A decoy receptor is a receptor that is able to recognize and bind specific

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regul ...

s or

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 autocrin ...

s efficiently, but is not structurally able to signal or activate the intended receptor complex. It acts as an inhibitor, binding a ligand and keeping it from binding to its regular receptor. Decoy receptors participate in a common methods of signal inhibition and are also abundant in malignant tissues, making up a significant topic in cancer research. Decoy Receptor Figure-raster

Examples

Interleukin 1 receptor type II

IL1R2 was one of the first identified decoy receptors. It binds IL1A and IL1B and inhibits their binding to IL1R1, deterring the inflammatory response which is generally promoted by the binding of type 1 interleukins to interleukin receptor 1 type I.

Decoy receptor 3 (DcR3)

Also known as TNFRSF6, the DcR3 receptor is found primarily in human malignant tissues. It acts as a decoy receptor for TNF cytokine members:

FasL Fas ligand (FasL or CD95L or CD178) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regula ...

, LIGHT, and TL1A, inhibiting the ability of the cytokines to signal for cell death or apoptosis.

VEGFR-1

VEGFR-1 is a kinase-defective receptor tyrosine kinase that negatively modulates angiogenesis by acting as a decoy receptor. The decoy characteristic of VEGFR-1 is required for normal development and angiogenesis. VEGFR-1 inhibits the activity of VEGFR-2 by sequestering VEGF, thus preventing VEGFR-2 from binding to VEGF.

Applications

Engineered Axl "decoy receptor"

Axl receptor tyrosine kinase has been associated with numerous diseases, most notably metastatic cancer. Axl has been shown to drive metastasis, confer therapeutic resistance and promote disease progression. Axl binds to its ligand, Gas6, and becomes activated. Decoy receptors are being designed that bind to Gas6 and prevent Axl activation.

ACE-031

ACE-031 is an engineered decoy receptor and myostatin inhibitor used in attempts to treat children with

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis follow ...

(DMD). The ACE-031 receptor circulates outside the muscle-fiber membrane. Because this receptor binds to

myostatin Myostatin (also known as growth differentiation factor 8, abbreviated GDF8) is a protein that in humans is encoded by the ''MSTN'' gene. Myostatin is a myokine that is produced and released by myocytes and acts on muscle cells to inhibit muscle ...

, it lowers the amount of myostatin that can bind to the native receptor in the membrane (ActRIIB), preventing myostatin from delivering the muscle growth-limiting signal.

References

External links

* * {{cite journal , doi=10.1016/S0955-0674(99)80034-9 , volume=11 , issue=2 , title=Apoptosis control by death and decoy receptors , journal=Current Opinion in Cell Biology , pages=255–260, date=April 1999 , last1=Ashkenazi , first1=Avi , last2=Dixit , first2=Vishva M. , pmid=10209153 Receptors