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Title: A comparative study of phosphoinositide and calcium signalling by G-protein-coupled receptors and growth factor receptors in human SH-SY5Y neuroblastoma cells
Authors: Wheldon, Lee Mark.
Award date: 2001
Presented at: University of Leicester
Abstract: This study investigated G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK)-mediated signal transduction via phospholipase C (PLC).;A transient elevation of intracellular [Ca2+] ([Ca2+]i) was identified in response to PDGF-BB. Despite the recruitment and phosphorylation of PLC-, the mechanism was apparently novel and Ins(1,4,5)P3-independent. Muscarinic M3 receptor-dependent Ins(1.4.5)P3 and Ca2+ signalling was biphasic, consisting of a peak and plateau. Both agonist-occupied receptors relied on capacitative Ca2+ influx triggered by intracellular Ca2+ store release for maximum elevation of [Ca2+]i and initiated intracellular Ca2+ release from the same thapsigargin and Ins(1,4,5)P3-sensitive intracellular store. This study demonstrated that activation of muscarinic M3 receptors abolished PDGF-mediated elevation of [Ca2+]i by depleting the intracellular store, whilst PDGF receptors inhibited subsequent muscarinic receptor-mediated elevation of [Ca2+]i, possibly by inhibition of PLC- isoform. Furthermore, a PDGF-mediated elevation of [Ca2+]i was also identified in differentiated SH-SY5Y cells and hippocampal neurons.;Muscarinic M3 receptors, PDGF receptors and epidermal growth factor (EGF) receptors activated mitogen-activated protein (MAP) kinase in SH-SY5Y cells. However, only PDGF-mediated MAP kinase activation had a Ca2+-dependent component suggesting that PDGF-mediated Ca2+ signalling may play other roles and an understanding of these functions emphasises the need to understand the mechanism of [Ca2+]i regulation by growth factor receptors in neurons.
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, Dept. of Cell Physiology and Pharmacology
Leicester Theses

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