| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
GROWTH FACTORS-CYTOKINES-ONCOGENES |
6ß1 and Cell Surface Heparan Sulfate Proteoglycans
Departments of Molecular Genetics (T.M.G., N.C., L.F.L.) and Pharmacology (S.C.-T.L.), University of Illinois at Chicago, Chicago, Illinois 60607-7170; and Center for Molecular Medicine (V.L.), Maine Medical Center Research Institute, Scarborough, Maine 04074
Address all correspondence and requests for reprints to: Lester F. Lau, Department of Molecular Genetics, University of Illinois at Chicago College of Medicine, 900 South Ashland Avenue, Chicago, Illinois 60607-7170. E-mail: . lflau{at}uic.edu
Cysteine-rich 61 (CYR61, CCN1) is a heparin-binding, extracellular, matrix-associated protein of the cysteine-rich 61/nephroblastoma family, which also includes connective tissue growth factor, nephroblastoma overexpressed, Wnt-induced secreted protein-1 (WISP-1), WISP-2, and WISP-3. CYR61 induces angiogenesis in vivo and supports cell adhesion, promotes cell migration, and enhances growth factor-stimulated mitogenesis in fibroblasts and endothelial cells. Although the expression of CYR61 has been observed in arterial walls, its function in vascular smooth muscle cells (VSMCs) has not been examined to date. Here we show that purified CYR61 supports VSMC adhesion in a dose-dependent, saturable manner through integrin 
6ß1 with an absolute requirement of cell surface heparan sulfate proteoglycans. In addition, CYR61 induces VSMC chemotaxis, but not chemokinesis, through integrin 6ß1 and heparan sulfate proteoglycans. Heparin-binding defective CYR61 mutants are unable to support VSMC adhesion but can still induce chemotaxis at a reduced level. Following balloon angioplasty in rat carotid artery, CYR61 protein level is elevated in the media and neointima of the injured vessel by d 4 post angioplasty, peaks from d 7 to 14, and remains high for at least 28 d. These data demonstrate the activities of CYR61 in VSMCs, identify the receptors that mediate its functions, and show that CYR61 is synthesized in arterial smooth muscle walls during proliferative restenosis. Together, these results implicate CYR61 as a novel factor that modulates the responses of VSMCs to vascular injury.
This article has been cited by other articles:
 |
|
 |
|
  M.-T. Lin, I-H. Kuo, C.-C. Chang, C.-Y. Chu, H.-Y. Chen, B.-R. Lin, M. Sureshbabu, H.-J. Shih, and M.-L. Kuo Involvement of Hypoxia-inducing Factor-1{alpha}-dependent Plasminogen Activator Inhibitor-1 Up-regulation in Cyr61/CCN1-induced Gastric Cancer Cell Invasion J. Biol. Chem., June 6, 2008; 283(23): 15807 - 15815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsumae, Y. Yoshida, K. Ono, K. Togi, K. Inoue, Y. Furukawa, Y. Nakashima, Y. Kojima, M. Nobuyoshi, T. Kita, et al. CCN1 Knockdown Suppresses Neointimal Hyperplasia in a Rat Artery Balloon Injury Model Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1077 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Papanicolaou, Y. Izumiya, and K. Walsh Forkhead Transcription Factors and Cardiovascular Biology Circ. Res., January 4, 2008; 102(1): 16 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Crockett, N. Schutze, D. Tosh, S. Jatzke, A. Duthie, F. Jakob, and M. J. Rogers The Matricellular Protein CYR61 Inhibits Osteoclastogenesis by a Mechanism Independent of {alpha}v{beta}3 and {alpha}v{beta}5 Endocrinology, December 1, 2007; 148(12): 5761 - 5768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-T. Lin, C.-C. Chang, B.-R. Lin, H.-Y. Yang, C.-Y. Chu, M.-H. Wu, and M.-L. Kuo Elevated Expression of Cyr61 Enhances Peritoneal Dissemination of Gastric Cancer Cells through Integrin {alpha}2beta1 J. Biol. Chem., November 23, 2007; 282(47): 34594 - 34604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Lee, J.-W. Chung, S.-W. Youn, J.-Y. Kim, K.-W. Park, B.-K. Koo, B.-H. Oh, Y.-B. Park, B. Chaqour, K. Walsh, et al. Forkhead Transcription Factor FOXO3a Is a Negative Regulator of Angiogenic Immediate Early Gene CYR61, Leading to Inhibition of Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia Circ. Res., February 16, 2007; 100(3): 372 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. McCallum, S. Price, N. Planque, B. Perbal, A. Pierce, A. D. Whetton, and A. E. Irvine A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation Blood, September 1, 2006; 108(5): 1716 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-Y. Tong and D. R Brigstock Intrinsic biological activity of the thrombospondin structural homology repeat in connective tissue growth factor. J. Endocrinol., March 1, 2006; 188(3): R1 - R8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Todorovicc, C.-C. Chen, N. Hay, and L. F. Lau The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts J. Cell Biol., November 7, 2005; 171(3): 559 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-T. Lin, C.-Y. Zuon, C.-C. Chang, S.-T. Chen, C.-P. Chen, B.-R. Lin, M.-Y. Wang, Y.-M. Jeng, K.-J. Chang, P.-H. Lee, et al. Cyr61 Induces Gastric Cancer Cell Motility/Invasion via Activation of the Integrin/Nuclear Factor-{kappa}B/Cyclooxygenase-2 Signaling Pathway Clin. Cancer Res., August 15, 2005; 11(16): 5809 - 5820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Lepore, T. P. Cappola, P. A. Mericko, E. E. Morrisey, and M. S. Parmacek GATA-6 Regulates Genes Promoting Synthetic Functions in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 309 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lindner, Q. Wang, B. A. Conley, R. E. Friesel, and C. P.H. Vary Vascular Injury Induces Expression of Periostin: Implications for Vascular Cell Differentiation and Migration Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 77 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Grote, U. Bavendiek, C. Grothusen, I. Flach, D. Hilfiker-Kleiner, H. Drexler, and B. Schieffer Stretch-inducible Expression of the Angiogenic Factor CCN1 in Vascular Smooth Muscle Cells Is Mediated by Egr-1 J. Biol. Chem., December 31, 2004; 279(53): 55675 - 55681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, D. J. Abraham, X. Shi-wen, J. D. Pearson, C. M. Black, K. M. Lyons, and A. Leask CCN2 (Connective Tissue Growth Factor) Promotes Fibroblast Adhesion to Fibronectin Mol. Biol. Cell, December 1, 2004; 15(12): 5635 - 5646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Chen, S.-J. Leu, V. Todorovic, S. C.-T. Lam, and L. F. Lau Identification of a Novel Integrin {alpha}v{beta}3 Binding Site in CCN1 (CYR61) Critical for Pro-angiogenic Activities in Vascular Endothelial Cells J. Biol. Chem., October 15, 2004; 279(42): 44166 - 44176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Leu, N. Chen, C.-C. Chen, V. Todorovic, T. Bai, V. Juric, Y. Liu, G. Yan, S. C.-T. Lam, and L. F. Lau Targeted Mutagenesis of the Angiogenic Protein CCN1 (CYR61): SELECTIVE INACTIVATION OF INTEGRIN {alpha}6{beta}1-HEPARAN SULFATE PROTEOGLYCAN CORECEPTOR-MEDIATED CELLULAR FUNCTIONS J. Biol. Chem., October 15, 2004; 279(42): 44177 - 44187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-T. Lin, C.-C. Chang, S.-T. Chen, H.-L. Chang, J.-L. Su, Y.-P. Chau, and M.-L. Kuo Cyr61 Expression Confers Resistance to Apoptosis in Breast Cancer MCF-7 Cells by a Mechanism of NF-{kappa}B-dependent XIAP Up-Regulation J. Biol. Chem., June 4, 2004; 279(23): 24015 - 24023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Baron, G. R. Bolduc, M. B. Goldberg, T. C. Auperin, and L. C. Madoff Alpha C Protein of Group B Streptococcus Binds Host Cell Surface Glycosaminoglycan and Enters Cells by an Actin-dependent Mechanism J. Biol. Chem., June 4, 2004; 279(23): 24714 - 24723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gao and D. R. Brigstock Connective Tissue Growth Factor (CCN2) Induces Adhesion of Rat Activated Hepatic Stellate Cells by Binding of Its C-terminal Domain to Integrin {alpha}v{beta}3 and Heparan Sulfate Proteoglycan J. Biol. Chem., March 5, 2004; 279(10): 8848 - 8855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. GROTENDORST, H. RAHMANIE, and M. R. DUNCAN Combinatorial signaling pathways determine fibroblast proliferation and myofibroblast differentiation FASEB J, March 1, 2004; 18(3): 469 - 479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Mason, A. C. Lake, J. E. Wubben, R. A. Nowak, and J. J. Castellot Jr The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells Mol. Hum. Reprod., March 1, 2004; 10(3): 181 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, A. Chen, D. De Leon, H. Li, E. Noiri, V. T. Moy, and M. S. Goligorsky Atomic force microscopy measurement of leukocyte-endothelial interaction Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H359 - H367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-W. Chen, M. J. Hubal, E. P. Hoffman, P. D. Thompson, and P. M. Clarkson Molecular responses of human muscle to eccentric exercise J Appl Physiol, December 1, 2003; 95(6): 2485 - 2494. [Abstract] [Full Text]
|
|
|
|
|
|
M. Kunz, S. Moeller, D. Koczan, P. Lorenz, R. H. Wenger, M. O. Glocker, H.-J. Thiesen, G. Gross, and S. M. Ibrahim Mechanisms of Hypoxic Gene Regulation of Angiogenesis Factor Cyr61 in Melanoma Cells J. Biol. Chem., November 14, 2003; 278(46): 45651 - 45660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Calzada, J. M. Sipes, H. C. Krutzsch, P. D. Yurchenco, D. S. Annis, D. F. Mosher, and D. D. Roberts Recognition of the N-terminal Modules of Thrombospondin-1 and Thrombospondin-2 by {alpha}6{beta}1 Integrin J. Biol. Chem., October 17, 2003; 278(42): 40679 - 40687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Leu, Y. Liu, N. Chen, C.-C. Chen, S. C.-T. Lam, and L. F. Lau Identification of a Novel Integrin {alpha}6{beta}1 Binding Site in the Angiogenic Inducer CCN1 (CYR61) J. Biol. Chem., September 5, 2003; 278(36): 33801 - 33808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Schober, L. F. Lau, T. P. Ugarova, and S. C.-T. Lam Identification of a Novel Integrin {alpha}M{beta}2 Binding Site in CCN1 (CYR61), a Matricellular Protein Expressed in Healing Wounds and Atherosclerotic Lesions J. Biol. Chem., July 3, 2003; 278(28): 25808 - 25815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Lin, S.-J. Leu, N. Chen, C. M. Tebeau, S.-X. Lin, C.-Y. Yeung, and L. F. Lau CCN3 (NOV) Is a Novel Angiogenic Regulator of the CCN Protein Family J. Biol. Chem., June 20, 2003; 278(26): 24200 - 24208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Soon, T.-A. Yie, A. Shvarts, A. J. Levine, F. Su, and K.-M. Tchou-Wong Overexpression of WISP-1 Down-regulated Motility and Invasion of Lung Cancer Cells through Inhibition of Rac Activation J. Biol. Chem., March 21, 2003; 278(13): 11465 - 11470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-E Mo, A. G. Muntean, C.-C. Chen, D. B. Stolz, S. C. Watkins, and L. F. Lau CYR61 (CCN1) Is Essential for Placental Development and Vascular Integrity Mol. Cell. Biol., December 15, 2002; 22(24): 8709 - 8720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Leu, S. C.-T. Lam, and L. F. Lau Pro-angiogenic Activities of CYR61 (CCN1) Mediated through Integrins alpha vbeta 3 and alpha 6beta 1 in Human Umbilical Vein Endothelial Cells J. Biol. Chem., November 22, 2002; 277(48): 46248 - 46255. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
