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G. Stanley McKnight

mcknight@u.washington.edu
Professor, Department of Pharmacology

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Cyclic AMP and Calcium Mediated Signal Transduction Protein kinases play an essential role in intracellular regulation by phosphorylating key substrates such as ion channels, enzymes, transcription factors, and cytoskeletal proteins. Phosphorylation can reversibly alter the biological activity of these substrates allowing a neuron to rapidly adapt to neurotransmitter and neuromodulator signals. Our laboratory is using the techniques of molecular genetics to study the cAMP and calcium regulated kinases that are expressed in brain. Mutant mice have been produced with targeted disruptions of each of the subunits of cAMP-dependent protein kinase (PKA) and we have focused our attention on the regulation of neural gene expression and behavioral responses to pharmacological manipulation of the dopamine system. Currently we are studying tissue-specific knockouts and point mutations in both the PKA genes and the calcium regulated kinase, CaMKIV. These knockout mice and others that are being created are expected to develop genetic diseases that will shed light on the normal physiological role of each kinase isoform in learning and behavior.

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