Smoothened
Encyclopedia
Smoothened is a G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 protein encoded by the gene of the hedgehog pathway conserved from flies
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

 to humans. It is the molecular target of the teratogen cyclopamine
Cyclopamine
Cyclopamine is a naturally occurring chemical that belongs to the group of steroidal jerveratrum alkaloids. It is a teratogen isolated from the corn lily that causes usually fatal birth defects. It can prevent the fetal brain from dividing into two lobes and cause the development of a single eye...

.

Cellular localization plays an essential role in the function of SMO. Stimulation of the patched
PTCH1
Protein patched homolog 1 is a protein that is the member of the Patched family and in humans is encoded by the PTCH1 gene.- Function :PTCH1 is a member of the patched gene family and is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in...

 receptor by the sonic hedgehog
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...

 ligand leads to translocation of SMO to the primary cilium
Cilium
A cilium is an organelle found in eukaryotic cells. Cilia are slender protuberances that project from the much larger cell body....

. Furthermore, SMO that is mutated in the domain required for ciliary localisation cannot contribute to pathway activation. SMO has also been shown to bind the kinesin
Kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule filaments, and are powered by the hydrolysis of ATP . The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular...

 motor protein Costal-2 and play a role in the localization of the Ci
Ci protein
Ci protein, short for Cubitus interruptus, is a zinc finger containing transcription factor involved in the Hedgehog signaling pathway. In the absence of a signal to the Hedgehog signaling pathway, the Ci protein is cleaved and destroyed in proteasomes...

 (Cubitus interruptus transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

) complex.

SMO can function as an oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...

. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.

See also

  • Frizzled
    Frizzled
    Frizzled is a family of G protein-coupled receptor proteins that serve as receptors in the Wnt signaling pathway and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled in the cytosol.-Species distribution:...

  • Vismodegib
    Vismodegib
    Vismodegib is an investigational drug for the treatment of various types of cancer. It has completed a Phase II clinical trial for metastasizing basal-cell carcinoma and is in Phase II trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer,...

    , a smoothened receptor inhibitor being investigated for the treatment of cancer

External links

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