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Where technology & law meet: Open Access research on data security & its regulation ...

Strathprints makes available Open Access scholarly outputs exploring both the technical aspects of computer security, but also the regulation of existing or emerging technologies. A research specialism of the Department of Computer & Information Sciences (CIS) is computer security. Researchers explore issues surrounding web intrusion detection techniques, malware characteristics, textual steganography and trusted systems. Digital forensics and cyber crime are also a focus.

Meanwhile, the School of Law and its Centre for Internet Law & Policy undertake studies on Internet governance. An important component of this work is consideration of privacy and data protection questions and the increasing focus on cybercrime and 'cyberterrorism'.

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Assessment of the extracellular and intracellular actions of sphingosine 1-phosphate by using the p42/p44 mitogen-activated protein kinase cascade as a model

Tolan, D and Conway, A M and Rakhit, S and Pyne, N and Pyne, S (1999) Assessment of the extracellular and intracellular actions of sphingosine 1-phosphate by using the p42/p44 mitogen-activated protein kinase cascade as a model. Cellular Signalling, 11 (5). pp. 349-354. ISSN 1873-3913

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Abstract

We have investigated the extracellular and intracellular actions of sphingosine 1-phosphate (S1P) by using cultured airway smooth muscle cells. We have demonstrated that exogenous S1P elicited an activation of mitogen activated protein kinase (p42/p44 MAPK) that was abolished by pertussis toxin (0.1 mu g/mL, 24 h), which was used to inactivate G(i). The effect of exogenous S1P might therefore be attributed to an action at a putative Gi-coupled receptor. The regulation of the p42/p44 MAPK cascade by S1P was also shown to include a protein kinase C (PKC)-dependent intermediate step. Platelet-derived growth factor (PDGF) stimulates intracellular S1P formation and was therefore used to evaluate the intracellular action of S1P. This has previously been investigated by others using the sphingosine kinase inhibitors D,L-threo-dihydrosphingosine and N,N-dimethylsphingosine. We have demonstrated here that both inhibitors block the PDGF-dependent activation of p42/p44 MAPK. However, both are also PKC inhibitors, which might account for their effect. because PDGF utilises PKC as an intermediate in the regulation of the p42/p44 MAPK cascade. Significantly, sphingosine, which is the substrate of sphingosine kinase and a PKC inhibitor, blocked the activation of p42/p44 MAPK by PDGF with an almost identical concentration dependence compared with D,L-threo-dihydrosphingosine and N,N-dimethylsphingosine. Therefore, the use of so-called sphingosine kinase inhibitors might lead to misleading interpretations because of their additional effect on PKC. Other approaches, such as oligodeoxynucleotide anti-sense against sphingosine kinase, are required to address the intracellular role of S1P. CELL SIGNAL 11;5:349-354, 1999.