THE ROLE OF THE PROLINE-RICH TYROSINE KINASE 2 PROTEIN IN THE REGULATION OF METABOTROPIC GLUTAMATE RECEPTOR SIGNALLING

Group I metabotropic glutamate receptors (mGluRs) - mGluRl and mGluR5 - are believed to contribute to neuronal death upon overstimulation and may be neuroprotective under other conditions. To develop treatment for mGluRs, we must identify proteins involved in their signalling. We have identified proline-rich tyrosine kinase 2 (Pyk2) as an mGluRl/5 interacting protein, and our objective was to investigate its contribution to the downstream activation of extracellular signal-regulated kinases (ERKs) by Group I mGluRs. In HEK 293 cells, ERK1/2 phosphorylation is greater in cells co-expressing mGluRl and wild-type Pyk2 than in cells expressing the receptor alone, and blocked in cells co-expressing the receptor and a dominant-negative mutant Pyk2. In cortical neurons, various inhibitors of endogenous Pyk2 block agonist stimulation of mGluRl-mediated ERK1/2 phosphorylation. Taken together, our data suggest wild-type Pyk2 is part of a cascade involved in enhancing ERK1∕2 activation by mGluRl.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Pharmacology and Toxicology

Year dc:date.issued

2008

Author dc:creator

• Nicodemo, Alexander A.

Advisors dc:contributor.advisor

• Ferguson, Stephen
• Rylett, Jane
• Meakin, Susan

• metabotropic glutamate receptor
• proline-rich tyrosine kinase 2
• extracellular signal-regulated kinase
• phosphorylation
• signalling
• cortical neurons

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/19565

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/19565