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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2091.)
© 2008 American Heart Association, Inc.

Editorials

"FRNKly, Smooth Muscle, I Don’t Give a CArG!"

A Novel Mechanism for Smooth Muscle Cell Differentiation

Julia A. Lemmon; Brian R. Wamhoff

From the Department of Medicine, Cardiovascular Division, Department of Pharmacology, The Laboratory of Atherogenesis, Robert M. Berne Cardiovascular Research Center, The University of Virginia, Charlottesville.

Correspondence to Brian Wamhoff, The University of Virginia, 409 Lane Road, Rm 6022, Charlottesville, VA 22908. E-mail wamhoff@virginia.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Studies spanning the last two decades have begun to uncover the molecular mechanisms underlying smooth muscle cell (SMC) differentiation, specifically the critical role of the ubiquitously expressed serum response factor (SRF) transcription factor. SRF selectively binds to conserved cis-regulatory "CArG box" elements, CC(A/T)₆GG consensus sequence, in the promoters or first introns of numerous smooth muscle-selective genes. The SMC contractile marker genes smooth muscle alpha actin (SMA), smooth muscle myosin heavy chain (SM-MHC), and smooth muscle 22 alpha (SM22) all require multiple CArG boxes for proper transcriptional activation. On SRF binding, the coactivator myocardin is recruited to the promoter through direct interaction with SRF and is required for expression of CArG containing SMC-selective genes.^1,2 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Sayers et al detail the in vivo regulation of a SMC-selective CArG-independent gene, focal adhesion kinase related nonkinase (FRNK), that plays a critical role in CArG-dependent contractile gene expression during SMC differentiation and after vascular injury.³

See accompanying article on page 2115

Unlike other muscle cell types, adult SMCs exist in a highly plastic nonterminally differentiated state. SMCs can assume a proliferative and migratory synthetic phenotype, allowing for both complete investment of the endothelial tube during vascular development and repair of the vessel wall after arterial injury. Various environmental cues direct SMCs to phenotypically modulate into a highly contractile state that is necessary for proper vascular function.⁴ Important to these processes is focal adhesion kinase (FAK) signaling, whereby integrins and growth factors stimulate the . . . [Full Text of this Article]

Related Article:

FRNK Expression Promotes Smooth Muscle Cell Maturation During Vascular Development and After Vascular Injury

Rebecca L. Sayers, Liisa J. Sundberg-Smith, Mauricio Rojas, Haruko Hayasaka, J. Thomas Parsons, Christopher P. Mack, and Joan M. Taylor
Arterioscler Thromb Vasc Biol 2008 28: 2115-2122. [Abstract] [Full Text] [PDF]