title: FRNK expression promotes smooth muscle cell maturation during vascular development and after vascular injury.
abstract: OBJECTIVE
  Smooth muscle cell (SMC) differentiation is a dynamic process that must be tightly regulated for proper vascular development and to control the onset of vascular disease. Our laboratory previously reported that a specific focal adhesion kinase (FAK) inhibitor termed FRNK (FAK Related Non-Kinase) is selectively expressed in large arterioles when SMCs are transitioning from a synthetic to contractile phenotype and that FRNK inhibits FAK-dependent SMC proliferation and migration. Herein, we sought to determine whether FRNK expression modulates SMC phenotypes in vivo.
  
  
  RESULTS
  We present evidence that FRNK(-/-) mice exhibit attenuated SM marker gene expression during postnatal vessel growth and after vascular injury. We also show that FRNK expression is regulated by transforming growth factor (TGF)-beta and that forced expression of FRNK in cultured cells induces serum- and TGF-beta-stimulated SM marker gene expression, whereas FRNK deletion or expression of a constitutively activated FAK variant attenuated SM gene transcription.
  
  
  CONCLUSIONS
  These data highlight the possibility that extrinsic signals regulate the SMC gene profile, at least in part, by modulating the expression of FRNK and that tight regulation of FAK activity by FRNK is important for proper SMC differentiation during development and after vascular injury.
authors.affiliation: Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Sayers
authors.forename: Liisa J
authors.initials: LJ
authors.lastname: Sundberg-Smith
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
authors.forename: Haruko
authors.initials: H
authors.lastname: Hayasaka
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Parsons
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Mack
authors.forename: Joan M
authors.initials: JM
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000254:growth & development / Q000293:injuries / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases
references.citation: Dev Cell. 2003 Jan;4(1):107-18
references.pmid: 12530967
references.citation: Dev Biol. 1996 Sep 15;178(2):375-92
references.pmid: 8812136
references.citation: Mol Cell Biol. 1997 Dec;17(12):6906-14
references.pmid: 9372922
references.citation: Mol Cell Biol. 2001 Mar;21(5):1565-72
references.pmid: 11238893
references.citation: Biochim Biophys Acta. 2002 Oct 21;1592(2):141-52
references.pmid: 12379477
references.citation: Mol Cell Biol. 1999 Sep;19(9):6120-9
references.pmid: 10454559
references.citation: Physiol Rev. 2004 Jul;84(3):767-801
references.pmid: 15269336
references.citation: J Mol Cell Cardiol. 2003 Jun;35(6):577-93
references.pmid: 12788374
references.citation: Cell Growth Differ. 1994 Aug;5(8):891-9
references.pmid: 7986754
references.citation: Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1675-83
references.pmid: 12791591
references.citation: J Cell Sci. 1999 Aug;112 ( Pt 16):2677-91
references.pmid: 10413676
references.citation: J Cell Sci. 2004 Jan 15;117(Pt 2):177-87
references.pmid: 14657279
references.citation: Biochem Biophys Res Commun. 2006 Sep 22;348(2):351-8
references.pmid: 16876108
references.citation: FASEB J. 2006 May;20(7):1006-8
references.pmid: 16585062
references.citation: J Cell Biol. 1998 May 4;141(3):805-14
references.pmid: 9566978
references.citation: J Clin Invest. 2000 Nov;106(9):1139-47
references.pmid: 11067866
references.citation: J Biol Chem. 2001 May 4;276(18):15378-85
references.pmid: 11278700
references.citation: Biochem J. 2002 Aug 1;365(Pt 3):591-603
references.pmid: 11988069
references.citation: Mol Genet Metab. 1999 Jan;66(1):24-30
references.pmid: 9973544
references.citation: Mol Cell Biol. 2004 May;24(9):3757-68
references.pmid: 15082771
references.citation: Am J Physiol Cell Physiol. 2004 Dec;287(6):C1560-8
references.pmid: 15306544
references.citation: J Biol Chem. 2004 Oct 8;279(41):42422-30
references.pmid: 15292266
references.citation: J Cell Biochem. 2005 Aug 15;95(6):1248-63
references.pmid: 15962314
references.citation: J Biol Chem. 2003 Aug 8;278(32):29783-91
references.pmid: 12782622
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Sep;289(3):R862-70
references.pmid: 15890789
references.citation: Circ Res. 2002 Apr 5;90(6):728-36
references.pmid: 11934842
references.citation: Blood. 1997 Oct 15;90(8):3073-81
references.pmid: 9376588
references.citation: J Cell Sci. 2003 Apr 15;116(Pt 8):1409-16
references.pmid: 12640026
references.citation: J Biol Chem. 2005 Nov 25;280(47):39534-44
references.pmid: 16157602
references.citation: Circ Res. 2001 Aug 3;89(3):211-23
references.pmid: 11485971
references.citation: J Mol Cell Cardiol. 2003 Dec;35(12):1407-20
references.pmid: 14654367
references.citation: Lab Invest. 1983 Sep;49(3):327-33
references.pmid: 6887785
references.citation: Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):2238-44
references.pmid: 9351395
references.citation: Circ Res. 2005 Nov 11;97(10):983-91
references.pmid: 16224064
references.citation: Int J Exp Pathol. 2000 Jun;81(3):173-82
references.pmid: 10971738
references.citation: Nat Neurosci. 2006 Oct;9(10):1274-83
references.pmid: 16964253