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Title: Activation of phospholipase D by the LHRH receptor and associated mechanisms
Author: Fennell, Myles
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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The αT3-1 gonadotroph-derived cell line was used as a model system to study intracellular signalling systems associated with the LHRH receptor, with particular interest in phospholipase D (PLD) and mechanisms involved in its regulation, such as protein kinase C (PKC) and non-receptor tryosine kinases. Phospholipase D activation in αT3-1 cells proceeded after a delay when stimulated by LHRH, or by the phorbol ester, phorbol 12,13-dibutyrate (PDBu). LHRH-stimulated PLD activity was fully resistant to desensitisation over a 40 min time course. The Ca2+ ionophore, ionomycin was unable to stimulate PLD activity. LHRH-stimulated PLD activity was inhibited by PKC downregulation or by bisindolylmaleimide PKC inhibitors at an approximately 8-fold higher concentration than that seen for the PDBu-stimulated PLD activity. Another PKC inhibitor, H7, inhibited PDBu-stimulated PLD activity in a manner that indicated multiple components to the inhibition and inhibited LHRH-stimulated PLD activity with a low potency. This is consistent with the possibility that one mediator of the LHRH response is a form of PKC which is relatively resistant to certain PKC inhibitors and insensitive to phorbol esters, or that some other unknown kinase is involved. The tyrosine kinase inhibitors, lavendustin A and genistein were able to selectively inhibit the LHRH-stimulated PLD activity. Phospholipase D activation stimulated by Gi and Go are involved. LHRH induced tyrosine phosphorylation of a number of proteins in αT3-1 cells; a similar phosphorylation profile was also produced by stimulation with PDBu.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available