DigitalCommons@Linfield

Cortactin and Aurora Kinase Localization in Cancer Cells

Jereld R. Nicholson Library

Cortactin is an actin binding protein upregulated in multiple cancer subtypes, including breast, neck, head, pancreatic, and others. A recent mass spectrometry report identified several previously studied as well as twelve novel serine, threonine, and tyrosine residues of cortactin phosphorylated in HEK293 cells (Martin, et al. Cortactin phosphorylation sites mapped by mass spectrometry. J Cell Sci. 2006 Jul 15;119(Pt 14):2851-3.). We report here that one of these residues, serine 384, is targeted by members of the Aurora kinase family. Aurora kinases are serine/threonine kinases involved in cell proliferation and have recently been implicated in the pediatric bone cancer Ewing’s Sarcoma under the downstream regulation of the EWS-FLI1 oncogenic fusion protein. We report in vitro and in situ data demonstrating cortactin as a serine target of the Aurora kinase. We show direct in vitro kinase assays demonstrating the phosphorylation of cortactin by aurora kinase. Treatment with kinase inhibitors also inhibits serine phosphorylation of cortactin in Vero cells. Future work will focus on the functional implications of this phosphorylation. This work was funded by a Medical Research Foundation Grant, a Linfield Faculty Student Collaborative Research Grant, and start-up funds from the M.J. Murdock Charitable Trust.