Date of Award


Degree Type


Degree Name

Master of Science


Pharmacology and Toxicology


Dr. Stephen Ferguson

Second Advisor

Dr. Jane Rylett

Third Advisor

Dr. Susan Meakin


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.



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