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Publication : Cortactin regulates cell migration through activation of N-WASP.

First Author  Kowalski JR Year  2005
Journal  J Cell Sci Volume  118
Issue  Pt 1 Pages  79-87
PubMed ID  15585574 Mgi Jnum  J:189997
Mgi Id  MGI:5447622 Doi  10.1242/jcs.01586
Citation  Kowalski JR, et al. (2005) Cortactin regulates cell migration through activation of N-WASP. J Cell Sci 118(Pt 1):79-87
abstractText  Cortactin is an actin-associated scaffolding protein that regulates cell migration. Amplification of the human gene, EMS1, has been detected in breast, head and neck tumors, where it correlates with increased invasiveness. Cortactin can regulate actin dynamics directly via its N-terminal half, which can bind and activate the Arp2/3 complex. The C-terminal portion of cortactin, however, is thought to have limited function in its regulation of the actin polymerization machinery. In this report, we identify a role for the cortactin C-terminus in regulating cell migration and, more specifically, actin dynamics. Overexpression of either full-length cortactin or cortactin C-terminus is sufficient to enhance migration of mammary epithelial cells. In vitro, cortactin binds to and activates, via its SH3 domain, a regulator of the Arp2/3 complex, neural Wiskott Aldrich Syndrome protein (N-WASP). This in vitro activation of N-WASP is likely to be important in vivo, as cortactin-enhanced migration is dependent upon N-WASP. Thus, our results suggest that cortactin has multiple mechanisms by which it can recruit and modulate the actin machinery and ultimately regulate cell migration.
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