Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parafollicular (PF) cells of the thyroid gland are neural crest derivatives, which costore the neurotransmitter, 5-hydroxytryptamine (5-HT) with calcitonin. PF cells are located adjacent to follicular (F) cells within the basement membrane of thyroid follicles. It has been proposed that 5-HT serves an intercellular signalling function in the thyroid and that F cells are its target. This proposal was tested by using cell lines derived from PF (medullary thyroid carcinoma [MTC]) and F (FRTL-5) cells to study the mechanisms that mediate the secretion and action of 5-HT. Secretion of 5-HT by MTC cells was evoked by thyroid stimulating hormone, thyrotropin (TSH), elevated extracellular calcium (increases [Ca2+]e), or by agents that increase intracellular cAMP (increases [cAMP]i). When protein kinase C (PKC) was down-regulated by prolonged treatment of MTC cells with phorbol 12-myristate 13-acetate (PMA), or PKC was inhibited by staurosporin, the TSH- or PMA-evoked secretion of 5-HT was blocked; however, interference with PKC function did not affect 5-HT secretion evoked by increases [Ca2+]e or increases [cAMP]i. In the putative targets, FRTL-5 cells, 5-HT increased the turnover of phosphoinositides (PI), cytosolic calcium (increases [Ca2+]i), increases [cAMP]i, and biphasically modified the effect of TSH on cAMP. All of these 5-HT effects were inhibited by 5-HT2 receptor antagonists (spiperone and ketanserin) and by pertussis toxin (PTx), suggesting that the actions of 5-HT are mediated by 5-HT2 receptors, which are coupled to a G protein. This suggestion was supported by the following additional observations: FRTL-5 membranes bound the 5-HT2 agonist, [125I]2,5-dimethoxy-4-iodophenylisopropylamine ([125I]-DOI), and anti-idiotypic antibodies, which recognize 5-HT2 receptors. [125I]-DOI binding was inhibited by guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) and the antibodies were displaced by spiperone. Data are consistent with the hypothesis that 5-HT serves as a PF to F cell messenger.
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PMID:Serotonergic signalling between thyroid cells: protein kinase C and 5-HT2 receptors in the secretion and action of serotonin. 133 23

To understand the genes and gene products involved in breast cancer invasion and metastasis, we previously isolated ten differentially expressed genes by differential cDNA library screening techniques, using the 13762NF rat mammary adenocarcinoma metastatic system. In this study, we further analysed a novel candidate metastasis-associated gene, mta1, previously designated clone 10.14. Northern blotting analyses showed that the steady-state mRNA expression level of mta1 was fourfold higher in a highly metastatic line (MTLn3) than in a nonmetastatic line (MTC.4). The mta1 gene was expressed at low levels in various normal rat organs, except testis, where it was expressed in high amounts. The mRNA expression levels of the human homologue of this gene were also examined in two human breast cancer metastatic systems; the ratios of mRNA were estimated to be MCF-7 (nonmetastatic):MCF7/LCC1 (invasive):MCF7/LCC2 (metastatic) = 1:2:4 and MDA-MB-468 (nonmetastatic):MDA231 (metastatic) = 1:4. Thus, the expression of this gene directly correlated with metastatic potential in two human systems, as well as in the rat metastatic system. Clone 10.14 was used to isolate a full-length cDNA clone for mta1, yielding the clone p10.14-C4.5, which was sequenced and analysed. Clone p10.14-C4.5 was 2756-bp long and contained a single open reading frame that could encode a protein of 703 amino acid (aa) residues. The aa sequence of mta1 was found to be novel by database homology search and contained possible phosphorylation sites for tyrosine kinase, protein kinase C and casein kinase II. A Pro-rich stretch was found at the C-terminal end that completely matched the consensus sequence for the SH3-binding motif.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of the complete sequence of the novel metastasis-associated candidate gene, mta1, differentially expressed in mammary adenocarcinoma and breast cancer cell lines. 760 77