UMMS Affiliation

Department of Cell Biology

Publication Date


Document Type



Alternative Splicing; Amino Acid Sequence; Animals; Aorta; Blotting, Western; COS Cells; Calcium-Binding Proteins; DNA, Complementary; Enzyme Activation; Ferrets; Glutathione Transferase; Membrane Proteins; Microfilament Proteins; Microscopy, Fluorescence; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Models, Genetic; Molecular Sequence Data; Muscle, Smooth; Oligonucleotides, Antisense; Phosphorylation; Protein Binding; Protein Kinase C; Protein Structure, Tertiary; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Signal Transduction; Subcellular Fractions; Time Factors; Transfection; Two-Hybrid System Techniques


Cell Biology | Life Sciences | Medicine and Health Sciences


The mechanisms by which protein kinase C (PKC) and extracellular-signal-regulated kinases (ERK1/2) govern smooth-muscle contractility remain unclear. Calponin (CaP), an actin-binding protein and PKC substrate, mediates signaling through ERK1/2. We report here that CaP sequences containing the CaP homology (CH) domain bind to the C-terminal 251 amino acids of smooth-muscle archvillin (SmAV), a new splice variant of supervillin, which is a known actin- and myosin-II-binding protein. The CaP-SmAV interaction is demonstrated by reciprocal yeast two-hybrid and blot-overlay assays and by colocalization in COS-7 cells. In differentiated smooth muscle, endogenous SmAV and CaP co-fractionate and co-translocate to the cell cortex after stimulation by agonist. Antisense knockdown of SmAV in tissue inhibits both the activation of ERK1/2 and contractions stimulated by either agonist or PKC activation. This ERK1/2 signaling and contractile defect is similar to that observed in CaP knockdown experiments. In A7r5 smooth-muscle cells, PKC activation by phorbol esters induces the reorganization of endogenous, membrane-localized SmAV and microfilament-associated CaP into podosome-like structures that also contain F-actin, nonmuscle myosin IIB and ERK1/2. These results indicate that SmAV contributes to the regulation of contractility through a CaP-mediated signaling pathway, involving PKC activation and phosphorylation of ERK1/2.

DOI of Published Version



J Cell Sci. 2004 Oct 1;117(Pt 21):5043-57. Epub 2004 Sep 21. Link to article on publisher's site

Journal/Book/Conference Title

Journal of cell science

Related Resources

Link to article in PubMed

PubMed ID




To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.