The smooth muscle-selective RhoGAP GRAF3 is a critical regulator of vascular tone and hypertension

Nature Communications

Volumn 4, Issue , 2013, Pages

  Bai, Xue ^a   Lenhart, Kaitlin C ^a   Bird, Kim E ^a   Suen, Alisa A ^a   Rojas, Mauricio ^a   Kakoki, Masao ^a   Li, Feng ^a   Smithies, Oliver ^a   MacK, Christopher P ^a   Taylor, Joan M ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; ANGIOTENSIN II; ENDOTHELIN 1; FASUDIL; GRAF3 PROTEIN; MYOSIN LIGHT CHAIN; PRAZOSIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; UNCLASSIFIED DRUG;

BLOOD; DISEASE INCIDENCE; DISEASE TREATMENT; HEALTH CARE; HEALTH SURVEY; HYPERTENSION; PRESSURE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD PRESSURE REGULATION; BLOOD VESSEL; BLOOD VESSEL TONE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPERTENSION; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; MUSCLE CONTRACTILITY; NONHUMAN; PRESSOR RESPONSE; PROTEIN ANALYSIS; PROTEIN DEPLETION; PROTEIN EXPRESSION ASSAY; PROTEIN PHOSPHORYLATION; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE;

MUS;

AMINO ACID SEQUENCE; ANGIOTENSIN II; ANIMALS; AORTA; BLOOD PRESSURE; BLOOD VESSELS; CELLS, CULTURED; FEMALE; GTPASE-ACTIVATING PROTEINS; HUMANS; HYPERTENSION; MALE; MICE; MICE, MUTANT STRAINS; MOLECULAR SEQUENCE DATA; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; MYOSIN LIGHT CHAINS; PHOSPHORYLATION; RATS; RHOA GTP-BINDING PROTEIN;

EID: 84890775992     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms3910     Document Type: Article

References (27)

1. Cowley, Jr A. W. The genetic dissection of essential hypertension. Nat. Rev. Genet. 7, 829-840 (2006).
2. Davis, M. J. et al. Integrins and mechanotransduction of the vascular myogenic response. Am. J. Physiol. Heart. Circ. Physiol. 280, H1427-H1433 (2001).
3. Davis, M. J. & Hill, M. A. Signaling mechanisms underlying the vascular myogenic response. Physiol. Rev. 79, 387-423 (1999). (Pubitemid 29210926)
4. Hall, J. E. The kidney, hypertension, and obesity. Hypertension 41, 625-633 (2003). (Pubitemid 36314565)
5. Lifton, R. P., Gharavi, A. G. & Geller, D. S. Molecular mechanisms of human hypertension. Cell 104, 545-556 (2001). (Pubitemid 32201949)
6. Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629-635 (2002). (Pubitemid 36764489)
7. Budzyn, K., Marley, P. D. & Sobey, C. G. Targeting Rho and Rho-kinase in the treatment of cardiovascular disease. Trends Pharmacol. Sci. 27, 97-104 (2006). (Pubitemid 43184031)
8. Loirand, G. & Pacaud, P. The role of Rho protein signaling in hypertension. Nat. Rev. Cardiol. 7, 637-647 (2010).
9. Amano, M. et al. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J. Biol. Chem. 271, 20246-20249 (1996). (Pubitemid 26281788)
10. Kimura, K. et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273, 245-248 (1996). (Pubitemid 26285892)
11. Mueller, B. K., Mack, H. & Teusch, N. Rho kinase, a promising drug target for neurological disorders. Nat. Rev. Drug Discov. 4, 387-398 (2005). (Pubitemid 40704122)
12. Wirth, A. et al. G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat. Med. 14, 64-68 (2008).
13. Masumoto, A. et al. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension 38, 1307-1310 (2001). (Pubitemid 34033407)
14. Guilluy, C. et al. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat. Med. 16, 183-190 (2010).
15. Kathiresan, S. & Srivastava, D. Genetics of human cardiovascular disease. Cell 148, 1242-1257 (2012).
16. Wain, L. V. et al. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nat. Genet. 43, 1005-1011 (2011).
17. International Consortium for Blood Pressure Genome Wide Association Studies. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103-109 (2011).
18. Hildebrand, J. D., Taylor, J. M. & Parsons, J. T. An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase. Mol. Cell. Biol. 16, 3169-3178 (1996). (Pubitemid 26163383)
19. Taylor, J. M., Macklem, M. M. & Parsons, J. T. Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho. J. Cell. Sci. 112(Pt 2): 231-242 (1999). (Pubitemid 29078357)
20. Taylor, J. M., Hildebrand, J. D., Mack, C. P., Cox, M. E. & Parsons, J. T. Characterization of graf, the GTPase-activating protein for rho associated with focal adhesion kinase. Phosphorylation and possible regulation by mitogenactivated protein kinase. J. Biol. Chem. 273, 8063-8070 (1998). (Pubitemid 28168858)
21. Doherty, J. T. et al. Skeletal muscle differentiation and fusion are regulated by the BAR-containing Rho-GTPase-activating protein (Rho-GAP), GRAF1. J. Biol. Chem. 286, 25903-25921 (2011).
22. Braunschweig, U., Gueroussov, S., Plocik, A. M., Graveley, B. R. & Blencowe, B. J. Dynamic integration of splicing within gene regulatory pathways. Cell 152, 1252-1269 (2013).
23. Ren, X. R. et al. Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein. J. Cell Biol. 152, 971-984 (2001).
24. Sundberg-Smith, L. J., DiMichele, L. A., Sayers, R. L., Mack, C. P. & Taylor, J. M. The LIM protein leupaxin is enriched in smooth muscle and functions as a serum response factor cofactor to induce smooth muscle cell gene transcription. Circ. Res. 102, 1502-1511 (2008).
25. Sayers, R. L. et al. FRNK expression promotes smooth muscle cell maturation during vascular development and after vascular injury. Arterioscler. Thromb. Vasc. Biol. 28, 2115-2122 (2008).
26. Mack, C. P. & Owens, G. K. Regulation of smooth muscle alpha-actin expression in vivo is dependent on CArG elements within the 5' and first intron promoter regions. Circ. Res. 84, 852-861 (1999). (Pubitemid 29181493)
27. Lockman, K. et al. Sphingosine 1-phosphate stimulates smooth muscle cell differentiation and proliferation by activating separate serum response factor co-factors. J. Biol. Chem. 279, 42422-42430 (2004). (Pubitemid 39372124)