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

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.

SUBMITTER: Kruchten AE

PROVIDER: S-EPMC2584996 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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

Kruchten Anne E AE Krueger Eugene W EW Wang Yu Y McNiven Mark A MA

American journal of physiology. Cell physiology 20080903 5

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 p ...[more]

PMID: 18768925

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Dataset Information

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

Publications

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

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