Distinct phospho-forms of cortactin differentially regulate actin polymerization and focal adhesions

Anne E. Kruchten, Eugene W. Krueger, Yu Wang, Mark A Mc Niven

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 phosphomimetic 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume295
Issue number5
DOIs
StatePublished - Nov 2008

Fingerprint

Cortactin
Focal Adhesions
Polymerization
Actins
Serine
Cell Movement
Tyrosine
Phosphorylation
Microfilament Proteins
Protein-Serine-Threonine Kinases
Cell Adhesion

Keywords

  • Cell migration
  • Phosphorylation

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Distinct phospho-forms of cortactin differentially regulate actin polymerization and focal adhesions. / Kruchten, Anne E.; Krueger, Eugene W.; Wang, Yu; Mc Niven, Mark A.

In: American Journal of Physiology - Cell Physiology, Vol. 295, No. 5, 11.2008.

Research output: Contribution to journalArticle

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