Smooth muscle archvillin: a novel regulator of signaling and contractility in vascular smooth muscle
AuthorsGangopadhyay, Samudra S.
Barber, Amy L.
Smith, Tara C.
Luna, Elizabeth J.
Morgan, Kathleen G.
UMass Chan AffiliationsDepartment of Cell Biology
Document TypeJournal Article
Amino Acid Sequence
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Molecular Sequence Data
Protein Kinase C
Protein Structure, Tertiary
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Two-Hybrid System Techniques
Medicine and Health Sciences
MetadataShow full item record
AbstractThe 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.
SourceJ Cell Sci. 2004 Oct 1;117(Pt 21):5043-57. Epub 2004 Sep 21. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/50784
Related ResourcesLink to article in PubMed
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