Faculty Publications

Publication Date

2008

Disciplines

Cellular and Molecular Physiology | Molecular Biology

Abstract

Cortactin is an actin-binding protein that is overexpressed in many cancers and is a substrate for both tyrosine and serine/threonine kinases. Tyrosine phosphorylation of cortactin has been observed to increase cell motility and invasion in vivo, although it has been reported to have both positive and negative effects on actin polymerization in vitro. In contrast, serine phosphorylation of cortactin has been shown to stimulate actin assembly in vitro. Currently, the effects of cortactin serine phosphorylation on cell migration are unclear, and furthermore, how the distinct phospho-forms of cortactin may differentially contribute to cell migration has not been directly compared. Therefore, we tested the effects of different tyrosine and serine phospho-mutants of cortactin on lamellipodial protrusion, actin assembly within cells, and focal adhesion dynamics. Interestingly, while expression of either tyrosine or serine phospho-mimetic cortactin mutants resulted in increased lamellipodial protrusion and cell migration, these effects appeared to be via distinct processes. Cortactin mutants mimicking serine phosphorylation appeared to predominantly affect actin polymerization, whereas mutation of cortactin tyrosine residues resulted in alterations in focal adhesion turnover. Thus these findings provide novel insights into how distinct phospho-forms of cortactin may differentially contribute to actin and focal adhesion dynamics to control cell migration.

Document Type

Published Version

Comments

This article is the publisher-created version, also considered to be the final version or the version of record. It includes value-added elements provided by the publisher, such as copy editing, layout changes, and branding consistent with the rest of the publication.

Rights

Copyright © 2008 the American Physiological Society

Original Citation

Anne E. Kruchten, Eugene W. Krueger, Yu Wang, & Mark A. McNiven
Distinct phospho-forms of cortactin differentially regulate actin polymerization and focal adhesions.
American Journal of Physiology-Cell Physiology, 2008, volume 295, issue 5, pages C1113-C1122
doi:10.1152/ajpcell.00238.2008

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