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AMP‐Activated Protein Kinase Reduces Vascular Smooth Muscle Growth by Inhibiting Actin Cytoskeleton Dynamics Necessary for Migration
Author(s) -
Stone Joshua Daniel,
Vuncan Jackson R,
Shaver Patti,
Fox Jonathan Clay,
Tulis David Anthony
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.870.28
Subject(s) - focal adhesion , microbiology and biotechnology , ampk , chemistry , cytoskeleton , actin cytoskeleton , actin , protein kinase a , cell migration , phosphorylation , biology , biochemistry , cell
Abluminal vascular smooth muscle cell (VSMC) migration is a functional underpinning of vasculoproliferative disorders. Upon activation, the dynamic nature of the actin cytoskeleton and rapid focal adhesion turnover provides the structural basis necessary for cell motility. Preliminary data show that activation of the metabolic sensor AMP‐activated protein kinase (AMPK) inhibits migration in rat primary VSMCs. In the current study we tested the hypothesis that AMPK enhances focal adhesion stability and inhibits vasodilator‐stimulated phosphoprotein (VASP) anti‐capping function on microfilament elongation. Treatment of VSMCs with the AMPK activator AICAR (1 mM) significantly (~50%; p<0.05) increased phosphorylated VASP at Thr278, a reported AMPK‐specific site, thus inhibiting microfilament anti‐capping by VASP. This inhibition of VASP was independent of the traditional VASP‐activating kinases PKA and PKG. In addition, AICAR inhibited PDGF‐stimulated autophosphorylation of focal adhesion kinase (FAK) at Ser397, a necessary event for kinase activity and focal adhesion turnover. Inhibition of phospho‐FAK at Ser397 induced focal adhesion stability necessary for cytostasis. These data lend strong support for the notion that AMPK has capacity to promote focal adhesion stability and to inhibit cytoskeletal rearrangement necessary for VSMC migration.