Intercellular calcium-mediated cell signaling in keratinocytes cultured from patients with NF1 or psoriasis
Abstract Neurofibromatosis type 1 syndrome (NF1) is caused by mutations of the NF1 gene. The NF1 protein (neurofibromin) contains a domain which is related to the GTPase-activating protein (GAP) and accelerates the switch of active Ras-GTP to inactive Ras-GDP. The NF1 protein has been referred...
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| Format: | Doctoral Thesis |
| Language: | English |
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University of Oulu
2002
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| Online Access: | http://urn.fi/urn:isbn:9514268040 http://nbn-resolving.de/urn:isbn:9514268040 |
| Summary: | Abstract
Neurofibromatosis type 1 syndrome (NF1) is caused by mutations of
the NF1 gene.
The NF1 protein (neurofibromin) contains a domain which is related to the GTPase-activating protein
(GAP) and accelerates the switch of active Ras-GTP to inactive Ras-GDP. The NF1 protein has been referred
to as a tumor suppressor, since the cells of malignant schwannomas of NF1 patients may display a loss
of heterozygosity of the NF1 gene. Psoriasis is characterized by hyperproliferation of the epidermis and by
down-regulated levels of NF1 mRNA and protein. Ca2+ is an universal signal
transduction element modulating cell growth and differentiation. Many cell types coordinate their activities by
transmitting waves of elevated intracellular calcium levels from cell to cell. The propagation of calcium
waves had not been studied previously in human keratinocytes. Thus, the aim of the present study was to
find out which pathways may play a role in
Ca2+ signaling at different extracellular
calcium concentrations in NF1 and and psoriatic keratinocytes versus
normal control keratinocytes.
The results demonstrated that NF1 and psoriatic keratinocytes have a tendency to form cultures characterized by altered
Ca2+-mediated cell signaling compared to normal keratinocytes. Specifically, the main route of
calcium-mediated signaling was gap-junctional in normal keratinocytes. In contrast, ATP-mediated calcium signaling predominated
and capacitative calcium influx was defective in NF1 and psoriatic keratinocytes.
The results of the present study suggest that mutations of the NF1 tumor
suppressor gene or lowered levels of NF1 protein/mRNA may eventually lead to altered intercellular communication.
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