Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study aimed to examine the distribution of 5-HT receptors in the human colon. 5-HT induces desensitization of the circular muscle and as this is facilitated by G-protein coupled receptor kinases (GRKs) and other proteins, we also examined their distribution. Human sigmoid colon samples were dissected into three separate layers (mucosa, taeniae coli and intertaenial strips) and RNA was amplified by RT-PCR. The 5-HT(2B) receptor and all 5-HT(7) receptor splice variants were expressed in all tissues. 5-HT(4) a,b,c and n splice variants were also expressed in all tissues and 5-HT(4d), 5-HT(4g) and 5-HT(4i) were only detected in some samples. The 5-HT(2A) receptor was seen predominantly in the intertaenial strips of the colon. Only one transcript of the serotonin transporter (SERT) was detected in the muscle layers. Variation was seen in GRK expression with GRK2 and 3 predominantly expressed in the mucosa, while GRK5 and 6 were found more commonly in the taeniae coli. PDZ (named after postsynaptic density protein, Drosophila disc large tumour suppressor and tight junction protein ZO-1) domain containing proteins, which may be involved in 5-HT receptor trafficking, were also detected throughout the sigmoid colon. The 5-HT(3A) subunit was expressed in all tissues, whereas the 5-HT(3E) subunit was mainly found in the mucosa layer while the 5-HT(3B) subunit was more common in the muscle layers. Receptor interacting chaperone (RIC-3), which is involved in transporting 5-HT(3) receptor subunits, is expressed less in mucosa compared to muscle layers. In conclusion, these results show that there is variation in distribution of 5-HT receptors and interacting proteins within the sigmoid colon that may contribute to colonic function.
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PMID:Distribution of serotonin receptors and interacting proteins in the human sigmoid colon. 1912 83

IgLONs are a family of four GPI-anchored cell adhesion molecules that regulate neurite outgrowth, synaptogenesis and may act as tumour suppressor genes. IgLONs are thought to function as monomers or homodimers and we have proposed that IgLONs also act as heterodimeric complexes termed Dimeric IgLONs or DIgLONs. Here we show that the initiation of neurite outgrowth is inhibited from a subset of chick embryonic day (E) 7 or 8 forebrain neurons when they are cultured on CHO cell lines expressing DIgLON:CEPU-1-OBCAM and DIgLON:CEPU-1-LAMP but not on CHO cells that express single IgLONs CEPU-1 or OBCAM. Surprisingly at the younger age of E6 forebrain neurons do not respond to DIgLONs. Since there is little difference in expression of IgLONs on the surface of chick forebrain neurons at these two ages we suggest IgLONs alone are not the receptor on the responding forebrain neurons. A DIgLON heterodimeric recombinant protein DIgLON:CEPU-1-OBCAM-Fc also blocked neurite outgrowth from E8 chick forebrain neurons. However, when IgLONs were removed from the surface of these E8 neurons they no longer responded to DIgLON:CEPU-1-OBCAM-Fc substrate, indicating that IgLONs form at least a component of the neuronal cell receptor complex involved in this inhibition of neurite outgrowth. Inhibitors pertussis toxin and Y27632 reversed the inhibition of neurite outgrowth on a DIgLON:CEPU-1-OBCAM and DIgLON:CEPU-1-LAMP substrate. This suggests the involvement of a G-protein coupled receptor and activation of Rho A. In summary we provide evidence that DIgLON:CEPU-1-OBCAM and DIgLON:CEPU-1-LAMP complexes regulate initiation of neurite outgrowth on forebrain neurons via an IgLON-containing receptor complex.
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PMID:DIgLONs inhibit initiation of neurite outgrowth from forebrain neurons via an IgLON-containing receptor complex. 2116 20

Novel genetic findings allow to more reliably elucidate the aetiology and pathogenesis of overgrowth syndromes in children and in adults. The relatively prevalent overgrowth syndromes in foetuses and neonates include Beckwith-Wiedemann (BWS) and Sotos syndromes; in addition, several rare conditions may occur e.g. Simpson-Golabi-Behmel and Weaver syndromes. These syndromes are not connected with overproduction of growth hormone. Their carriers are at risk of hypoglycaemia (in BWS), of congenital malformations and of childhood tumours. Targeted oncologic screening may improve the outcomes. Despite rapid growth even postnatally, the final height is mostly normal. In childhood and adolescence, the increased growth velocity results from hormonal overproduction - of precocious production of sexual hormones, hyperthyroidism, or of growth hormone overproduction due to pituitary adenoma that may lead to gigantism or acrogigantism and may be familiar (familiar isolated pituitary adenoma; FIPA). In 15-25 % of affected families, FIPA is caused by autosomal dominantly inherited mutations of AIP gene encoding a tumour suppressor protein named AIP (aryl hydrocarbon receptor-interacting protein). X-linked acrogigantism (X-LAG) is due to GPR101 gene mutations or microduplications of Xq26 chromosomal region. GPR101 encodes G-protein coupled receptor with unknown ligand. X-LAG is associated with recurrent and highly-penetrant pituitary macroadenomas. Mutations of additional at least 10 genes may lead to pituitary tumour with growth hormone overproduction. Gigantism in adults results from untreated or insufficiently treated pituitary adenoma in childhood. Some of the well-known current or past giants were found to carry pathogenic genetic variants of GPR101 or AIP.
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PMID:[Overgrowth in children and in adults: novel clinical view, novel genes, novel phenotypes]. 2899 7