Open AccessThe pro‐apoptotic protein Par‐4 facilitates vascular contractility by cytoskeletal targeting of ZIPK
Author(s) -
Vetterkind Susanne,
Morgan Kathleen G.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00374.x
Subject(s) - myosin , myosin light chain kinase , microbiology and biotechnology , actin , biology , phosphorylation , vascular smooth muscle , contractility , cytoskeleton , cell , biochemistry , endocrinology , smooth muscle
Par‐4 (prostate apoptosis response 4) is a pro‐apoptotic protein and tumour suppressor that was originally identified as a gene product up‐regulated during apoptosis in prostate cancer cells. Here, we show, for the first time, that Par‐4 is expressed and co‐localizes with the actin filament bundles in vascular smooth muscle. Furthermore, we demonstrate that targeting of ZIPK to the actin filaments, as observed upon PGF‐2α stimulation, is inhibited by the presence of a cell permeant Par‐4 decoy peptide. The same decoy peptide also significantly inhibits PGF‐2α induced contractions of smooth muscle tissue. Moreover, knockdown of Par‐4 using antisense morpholino nucleotides results in significantly reduced contractility, and myosin light chain and myosin phosphatase target subunit phosphorylation. These results indicate that Par‐4 facilitates contraction by targeting ZIPK to the vicinity of its substrates, myosin light chain and MYPT, which are located on the actin filaments. These results identify Par‐4 as a novel regulator of myosin light chain phosphorylation in differentiated, contractile vascular smooth muscle.