Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells

Zhizhan Gu, Jolanta Kordowska, Geoffrey L. Williams, C. L Albert Wang, Chi Ming Hai

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We tested the hypothesis that the MEK/Erk/caldesmon phosphorylation cascade regulates PKC-mediated podosome dynamics in A7r5 cells. We observed the phosphorylation of MEK, Erk and caldesmon, and their translocation to the podosomes upon phorbol dibutyrate (PDBu) stimulation, together with the nuclear translocation of phospho-MEK and phospho-Erk. After MEK inhibition by U0126, Erk translocated to the interconnected actin-rich columns but failed to translocate to the nucleus, suggesting that podosomes served as a site for Erk phosphorylation. The interconnected actin-rich columns in U0126-treated, PDBu-stimulated cells contained α-actinin, caldesmon, vinculin, and metalloproteinase-2. Caldesmon and vinculin became integrated with F-actin at the columns, in contrast to their typical location at the ring of podosomes. Live-imaging experiments suggested the growth of these columns from podosomes that were slow to disassemble. The observed modulation of podosome size and life time in A7r5 cells overexpressing wild-type and phosphorylation-deficient caldesmon-GFP mutants in comparison to untransfected cells suggests that caldesmon and caldesmon phosphorylation modulate podosome dynamics in A7r5 cells. These results suggest that Erk1/2 and caldesmon differentially modulate PKC-mediated formation and/or dynamics of podosomes in A7r5 vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)849-866
Number of pages18
JournalExperimental Cell Research
Volume313
Issue number5
DOIs
StatePublished - Mar 10 2007
Externally publishedYes

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Calmodulin-Binding Proteins
Vascular Smooth Muscle
Smooth Muscle Myocytes
Mitogen-Activated Protein Kinase Kinases
Phosphorylation
Vinculin
Actins
Actinin
Podosomes
Metalloproteases

Keywords

  • Actin
  • Adhesion
  • Atherosclerosis
  • Cytoskeleton
  • Metalloproteinase
  • Remodeling

ASJC Scopus subject areas

  • Cell Biology

Cite this

Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells. / Gu, Zhizhan; Kordowska, Jolanta; Williams, Geoffrey L.; Wang, C. L Albert; Hai, Chi Ming.

In: Experimental Cell Research, Vol. 313, No. 5, 10.03.2007, p. 849-866.

Research output: Contribution to journalArticle

Gu, Zhizhan ; Kordowska, Jolanta ; Williams, Geoffrey L. ; Wang, C. L Albert ; Hai, Chi Ming. / Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells. In: Experimental Cell Research. 2007 ; Vol. 313, No. 5. pp. 849-866.
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