Regulation of glioma cell migration by serine-phosphorylated P311

Wendy S. McDonough, Nhan Tran, Michael E. Berens

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

P311, an 8-kDa polypeptide, was previously shown to be highly expressed in invasive glioma cells. Here, we report the functional characteristics of P311 with regard to influencing glioma cell migration. P311 is constitutively serine-phosphorylated; decreased phosphorylation is observed in migration-activated glioma cells. The primary amino acid sequence of P311 indicates a putative serine phosphorylation site (S59) near the PEST domain. Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration. Coimmunoprecipitation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis identified Filamin A as a binding partner of P311, and immunofluorescence studies showed that both proteins colocalized at the cell periphery. Moreover, P311-induced cell migration was abrogated by inhibition of β1 integrin function using TACβ1A, a dominant-negative inhibitor of β1 integrin signaling, suggesting that P311 acts downstream of β1 signaling. Finally, overexpression of P311 or P311 S59A mutant protein activates Rac1 GTPase; small interfering RNA-mediated depletion of Rac1 suppresses P311-induced motility. Collectively, these results suggest a role for levels of P311 in regulating glioma motility and invasion through the reorganization of actin cytoskeleton at the cell periphery.

Original languageEnglish (US)
Pages (from-to)862-872
Number of pages11
JournalNeoplasia
Volume7
Issue number9
DOIs
StatePublished - Sep 2005
Externally publishedYes

Fingerprint

Glioma
Serine
Cell Movement
Integrins
Phosphorylation
Filamins
GTP Phosphohydrolases
Mutant Proteins
Site-Directed Mutagenesis
Actin Cytoskeleton
Small Interfering RNA
Fluorescent Antibody Technique
Amino Acid Sequence
Mass Spectrometry
Lasers
Peptides
Mutation
Proteins

Keywords

  • Glioma
  • Integrin
  • Migration
  • P311
  • Phosphorylation

ASJC Scopus subject areas

  • Cancer Research

Cite this

Regulation of glioma cell migration by serine-phosphorylated P311. / McDonough, Wendy S.; Tran, Nhan; Berens, Michael E.

In: Neoplasia, Vol. 7, No. 9, 09.2005, p. 862-872.

Research output: Contribution to journalArticle

McDonough, Wendy S. ; Tran, Nhan ; Berens, Michael E. / Regulation of glioma cell migration by serine-phosphorylated P311. In: Neoplasia. 2005 ; Vol. 7, No. 9. pp. 862-872.
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