University of Cambridge > > MRC LMB Seminar Series > Structural Studies on the Regulation of Protein Kinases: EGFR and CamK-II

Structural Studies on the Regulation of Protein Kinases: EGFR and CamK-II

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In this lecture I will discuss our recent analyses of two protein kinases. The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in cell growth that is often misregulated in cancer. We have elucidated the important role that the juxtamembrane segment and transmembrane helix of the receptor play in stabilizing an activating asymmetric dimer of the kinase domains, and I will discuss how these features allows specificity in signal transduction. Calcium/calmodulin dependent kinase II (CaMKII) forms a highly conserved dodecameric assembly that is sensitive to the frequency of calcium pulse trains. We have determined the crystal structure of an autoinhibited full-length human CaMKII holoenzyme, revealing an unexpected compact arrangement of kinase domains docked against a central hub, with the calmodulin binding site completely inaccessible. Our studies suggest a simple mechanism for tuning the calcium response without changes in either the hub or the kinase domains.

This talk is part of the MRC LMB Seminar Series series.

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