Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person Smoothened (Smo) is usually classified with family B GPCRs b...
| Class:Id | Summation:445099 |
|---|---|
| _displayName | Smoothened (Smo) is usually classified with family B GPCRs b... |
| _timestamp | 2010-02-19 10:37:39 |
| created | [InstanceEdit:445098] Jupe, S, 2009-10-27 |
| literatureReference | [LiteratureReference:445128] The cell biology of Smo signalling and its relationships with GPCRs [LiteratureReference:517470] Sonic hedgehog signaling by the patched-smoothened receptor complex [LiteratureReference:216183] Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened [LiteratureReference:208159] Regulation of Hedgehog signaling: a complex story [LiteratureReference:208377] Communicating with Hedgehogs |
| modified | [InstanceEdit:445148] Jupe, S, 2009-10-28 [InstanceEdit:517472] Jupe, S, 2010-02-18 [InstanceEdit:517513] Jupe, S, 2010-02-19 |
| text | Smoothened (Smo) is usually classified with family B GPCRs based on homology. There are indications that it can signal via G-proteins Gi and G12/13 (Ruiz-Gomez, 2007) but this role is poorly understood. It's better characterised physiological role is as the transducer of hedgehog (HH) signaling. In this capacity Smo is not acting as a receptor, but as part of a signaling cascade.
The Hedgehog(HH)/Smo signalling pathway was identified as a key component of Drosophila development and subsequently found to be conserved in all meatazoans. Most of the functions attributed to Smo are associated with development such as digit patterning in the chick limb bud and left–right asymmetry of vertebrate embryos. In addition, Smo appears to be involved in homeostasis; deregulated Smo signaling is implicated in tumorogenesis (Ruiz-Gomez, 2007). The ligand of the 12 transmembrane-domain receptor Patched (Ptc) is Hedgehog(HH) but in the absence of HH, Ptc binds Smo (Stone et al. 1996) which consequently becomes internalised into endosomes, where it associates with Costal-2 (Cos2), and lysosomes, where it is degraded. This 'inactivates' Smo by preventing the formation of an active Smo signaling complex at the plasma membrane. Internalised Smo:Cos2 forms a complex with protein kinase A (PKA), casein kinase I (CKI) glycogen synthase kinase-3 (GSK3) and Cucurbitus interruptus (Ci), a transcriptional regulator, enabling phosphorylation of Ci and subsequent processing to a transcriptional repressor form (CiR). When HH binds to Ptc, it does not bind Smo, allowing Smo to undergo a conformational change, exposing a new surface in its cytoplasmic tail. This causes PKA, CKI and GSK3 to dissociate from Smo:Cos2 complexes, so that Ci is no longer phosphorylated or processed to CiR. Accumulating Smo is phosphorylated instead and assumes a third conformational state. Phosphorylated Smo trafficks to the plasma membrane (Denef et al. 2000) and assembles into a signalling complex that promotes the phosphorylation of Fused (Fu) and Cos2. Phosphorylated Cos2 dissociates from membranes and recruits Fu to Sufu (Suppressor of Fused), which produces the activated form of Ci (CiA), probably through phosphorylation of Sufu (Hooper & Scott, 2005). |
| (summation) | [Reaction:445124] Patched binds Smoothened [Homo sapiens] [Reaction:517521] Patched binds Smoothened [Mus musculus] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by Smoothened (Smo) is usually classified with family B GPCRs b... (445099)
