G protien-coupled receptors go extracellular: RhoA integrates the integrins

Molecular Interventions

Volumn 8, Issue 4, 2008, Pages 165-173

  Walsh, Colin T ^a   Stupack, Dwayne ^b   Brown, Joan Heller ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE RICH PROTEIN 61; G PROTEIN COUPLED RECEPTOR; INTEGRIN; LYSOPHOSPHATIDIC ACID; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; SPHINGOSINE 1 PHOSPHATE; THROMBIN; SIGNAL PEPTIDE;

CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; CELL SURFACE; CELL SURVIVAL; ENZYME ACTIVATION; EXTRACELLULAR MATRIX; HUMAN; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; EXTRACELLULAR SPACE; METABOLISM;

ANIMALS; EXTRACELLULAR SPACE; HUMANS; INTEGRINS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; RECEPTORS, G-PROTEIN-COUPLED; RHOA GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION;

EID: 53549119691     PISSN: 15340384     EISSN: 15432548     Source Type: Journal    
DOI: 10.1124/mi.8.4.8     Document Type: Review

References (71)

1. Kireeva, M.L., Mo, F.E., Yang, G.P., and Lau, L.F. Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion. Mol. Cell. Biol. 16, 1326-1334 (1996).
2. Lau, L.F. and Lam, S.C. The CCN family of angiogenic regulators: The integrin connection. Exp. Cell Res. 10, 44-57 (1999).
3. Kolesnikova, T.V. and Lau, L.F. Human CYR61-mediated enhancement of ?FGF-induced DNA synthesis in human umbilical vein endothelial cells. Oncogene 16, 747-754 (1998).
4. Schwartz, M.A. and Shattil, S.J. Signaling networks linking intergrins and Rho family GTPasas. Trends Biochem. Sci. 8, 388-491 (2000).
5. Ilic, D., Furuta, Y., Kanazawa, S. et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 12,539-544 (1995).
6. Ridley, A.J. Rho GTPases and cell migration. J. Cell Sci. 114, 2713-2722 (2001).
7. Kaibuchi, K., Kuroda, S., and Amano, M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu. Rev. Biochem. 68, 459-486 (1999).
8. Sahai, E. and Marshall, C. RHO-GTPases and cancer. Nature Rev. Cancer 2, 133-142 (2002).
9. 12/13 and are able to activate RhoA, thereby eliciting contractile and cytoskeletal responses and modulating gene expression and cell proliferation.
10. Zohn, I.M., Campbell, S.L., Khosravi-Far, R., Rossman, K.L., and Der, C.J. Rho family proteins and Ras transformation: The RHOad less traveled gets congested. Oncogene 17, 1415-1438 (1998).
11. Kranenburg, O., Poland, M., van Horck, F.P.G., Drechsel, D., Hall, A., and Moolenaar, W.H. Activation of RhoA by lysophosphatidic acid and Ga12/13 subunits in neuronal cells: Induction of neurite retraction. Mol. Biol. Cell 10, 1851-1857 (1999).
12. Klages, B., Brandt, U., Simon, M.I., Schultz, G., and Offermanns, S. Activation of G12/G13 results in shape change and Rho/Rho kinase-mediated myosin light chain phosphorylation in mouse platelets. J. Cell. Biol. 144, 745-754 (1999).
13. 13 but not G12 mediates signaling from lysophosphatidic acid receptor via epidermal growth factor receptor to Rho. J. Biol. Chem. 273, 4653-4659 (1998).
14. Yonemura, S., Matsui, T., Tsukita, S., and Tsukita, S.Rho-dependent and -independent activation mechanisms of ezrin/radixin/moesin proteins: An essential role for polyphosphoinositides in vivo. J. Cell. Sci. 115, 2569-2580 (2002).
15. Seasholtz, T.M., Radeff-Huang, J., Sagi, S.A. et al. Rho-mediated cytoskeletal rearrangement in response to LPA is functionally antagonized by Rac1 and PIP2. J. Neurochem. 91, 501-512 (2004).
16. 12/13 and RhoA signaling was demonstrated.
17. Radeff-Huang, J., Seasholtz, T. M., Matteo, R.G., and Brown, J.H. G protein-mediated signaling pathways in lysophospholipid-induced cell proliferation and survival. J. Cell. Biochem. 92, 949-966 (2004).
18. Martin, C.B., Mahon, G.M., Kinger, M.B. et al. The thrombin receptor, PAR-1, causes transformation by activation of Rho-mediated signaling pathways. Oncogene 20, 1953-1963 (2001).
19. O'Brien, T.P., Yang, G.P., Sanders, L., and Lau, L.F. Expression of cyr61, a growth factor-inducible immediate-early gene. Mol. Cell Biol. 10, 3569-3577 (1990).
20. Brigstock, D.R. The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family. Endocr. Rev. 20, 189-206 (1999).
21. Perbal, B. NOV (nephroblastoma overexpressed) and the CCN family of genes: Structural and functional issues. Mol. Pathol. 54, 57-79 (2001).
22. Chen, N., Leu, S.J., Todorovic, V., Lam, S.C., and Lau, L.F. Identification of a novel integrin alphavbeta3 binding site in CCN1 (CYR61) critical for pro-angiogenic activities in vascular endothelial cells. J. Biol. Chem. 279, 44166-44176 (2004).
23. Leu, S.J., Liu, Y., Chen, N., Chen, C.C., Lam, S.C., and Lau, L.F. Identification of a novel integrin alpha 6 beta 1 binding site in the angiogenic inducer CCN1 (CYR61). J. Biol. Chem. 278, 33801-33808 (2003).
24. Schober, J.M., Lau, L.F., Ugarova, T.P., and Lam, S.C. Identification of a novel integrin alphaMbeta2 binding site in CCN1 (CYR61), a matricellular protein expressed in healing wounds and atherosclerotic lesions. J. Biol. Chem. 278, 25808-25815 (2003).
25. Chen, N., Chen, C.C., and Lau, L.F. Adhesion of human skin fibroblasts to Cyr61 is mediated through integrin alpha 6beta 1 and cell surface heparan sulfate proteoglycans. J. Biol. Chem. 275, 24953-24961 (2000).
26. Babic, A.M., Chen, C.C., and Lau, L.F. Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo. Mol. Cell. Biol. 19, 2958-2966 (1999).
27. Lau, L.F. and Lam, S.C.T. Integrated-mediated CCN functions, in CCN Proteins: A New Family of Cell Growth and Differentiation Regulators (Perbal, B. and Takigawa, M., eds) pp61-79, Imperial College Press, London, (2005).
28. Schober, J.M., Chen, N., Grzeszkiewicz, T.M. et al. Identification of integrin alpha(M)beta(2) as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2): Immediate-early gene products expressed in atherosclerotic lesions. Blood 99, 4457-4465 (2002).
29. Grzeszkiewicz, T.M., Kirschling, D.J., Chen, N., and Lau, L.F. CYR61 stimulates human skin fibroblast migration through integrin alpha vbeta 5 and enhances mitogenesis through integrin alpha vBeta 3, independent of its carboxyl-terminal domain. J. Biol. Chem. 276, 21943-21950 (2001).
30. Grzeszkiewicz, T.M., Lindner, V., Chen, N., Lam, S.C., and Lau, L.F. The angiogenic factor cysteine-rich 61 (CYR61, CCN1) supports vascular smooth muscle cell adhesion and stimulates chemotaxis through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans. Endocrinology 143, 1441-1450 (2002).
31. Ruoslahti, E. RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. 12, 697-715 (1996).
32. Chen, Y. and Du, X.Y. Functional properties and intracellular signaling of CCN1/Cyr61. J. Cell. Biochem. 100, 1337-1345 (2007).
33. Pendurthi, U.R., Allen, K.E., Ezban, M., and Rao, L.V. Factor VIIa and thrombin induce the expression of Cyr61 and connective tissue growth factor, extracellular matrix signaling proteins that could act as possible downstream mediators in factor VIIa x tissue factor-induced signal transduction. J. Biol. Chem. 275, 14632-14641 (2000).
34. Nguyen, N., Kuliopulos, A., Graham, R.A., and Covic, L. Tumor-derived Cyr61(CCN1) promotes stromal matrix metalloproteinase-1 production and protease-activated receptor 1-dependent migration of breast cancer cells. Cancer Res. 66, 2658-2665 (2006).
35. Pendurthi, U.R., Ngyuen, M., Andrade-Gordon, P., Petersen, L.C., and Rao, L.V. Plasmin induces Cyr61 gene expression in fibroblasts via protease-activated receptor-1 and p44/42 mitogen-activated protein kinase-dependent signaling pathway. Arterioscler. Thromb. Vasc. Biol. 22, 1421-1426 (2002).
36. Liang, Y., Li, C., Guzman, V.M et al. Comparison of prostaglandin F2alpha, bimatoprost (prostamide), and butaprost (EP2 agonist) on Cyr61 and connective tissue growth factor gene expression. J. Biol. Chem. 278, 27267-2777 (2003).
37. Hilfiker, A., Hilfiker-Kleiner, D., Fuchs, M. et al. Expression of CYR61, an angiogenic immediate early gene, in arteriosclerosis and its regulation by angiotensin II. Circulation 106, 254-260 (2002).
38. Hilfiker-Kleiner, D., Kaminski, K., Kaminska, A. et al. Regulation of proangiogenic factor CCN1 in cardiac muscle: Impact of ischemia, pressure overload, and neurohumoral activation. Circulation 109, 2227-2233 (2004).
39. Han, J.S., Macarak, E., Rosenbloom, J., Chung, K.C., and Chaqour, B. Regulation of Cyr61/CCN1 gene expression through RhoA GTPase and p38MAPK signaling pathways. Eur. J. Biochem. 270, 3408-3421 (2003).
40. Young, N. and van Brocklyn, J.R. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness. Exp. Cell. Res. 313, 1615-1627 (2007).
41. Sakamoto, S., Yokoyama, M., Zhang, X. et al. Increased expression of CYR61, an extracellular matrix signaling protein, in human benign prostatic hyperplasia and its regulation by lysophosphatidic acid. Endocrinology 145, 2929-2940 (2004).
42. Wiedmaier, N., Muller, S., Koberle, M. et al. Bacteria induce CTGF and CYR61 expression in epithelial cells in a lysophosphatidic acid receptor-dependent manner. Int. J. Med. Microbiol. 298, 231-243 (2008).
43. Walsh, C.T., Radeff-Huang, J., Matteo, R. et al. Thrombin receptor and RhoA mediate cell proliferation through integrins and cysteine-rich protein 61 (Cyr61/CCN1). FASEB J. Epub ahead of print; doi: 10.1096/fj.08-113266 (2008). Using microarray experiments we identified Cyr61/CCN1 as a gene induced in response to PAR1 thrombin but not muscarinic receptor activation. Here we demonstrate that this gene is upregulated through RhoA signaling, is secreted, and associates with the cell surface where it binds integrins. Using siRNA to block Cyr61 expression, and applying heparin or antibodies to integrin and Cyr61 outside the cell, we demonstrate that Cyr61 plays a critical role as a mediator of thrombin-stimulated DNA synthesis.
44. Trejo, J., Chambard, J.-C., Karin, M., and Brown, J.H. Biphasic increase in c-jun mRNA is required for induction of AP-1 mediated gene transcription: Differential effects of muscarinic and thrombin receptor activation. Mol. Cell. Biol. 12, 4742-4750 (1992). This paper reports our first evidence that muscarinic and thrombin receptors, which induce comparable acute activation of phospholipase C and its second messengers in 1321N1 glioblastoma cells, differentially regulate cJun- and AP-1-mediated gene expression. Subsequent studies showed that only thrombin induces mitogenesis in these cells.
45. Majumdar, M., Seasholtz, T.M., Goldstein, D., de Lanerolle, P., and Brown, J.H. Requirement for Rho-mediated myosin light chain phosphorylation in thrombin-stimulated cell rounding and its dissociation from mitogenesis. J. Biol. Chem. 273, 10099-10106 (1998).
46. Post, G.R., Collins, L.R., Kennedy, E.D. et al. Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells. Mol. Biol. Cell 7, 1679-1690 (1996).
47. Ishii, I., Ye, X., Friedman, B. et al. Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P2/LPB2/EDG-5 and S1P3/LPB3/EDG-3. J. Biol. Chem. 277, 25152-25159 (2002).
48. Hilal-Dandan, R., Means, C.K., Gustafsson, A.B. et al. Lysophosphatidic acid induces hypertrophy of neonatal cardiac myocytes via activation of Gi and Rho. J. Mol. Cell. Cardiol. 36, 481-493 (2004).
49. Shao, F., Merrit, P.M., Bao, Z., Innes, R.W., and Dixon, J.E. A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell 109, 575-588 (2002).
50. Si, W., Kang, Q., Luu, H.H. et al. CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells. Mol. Cell. Biol. 26, 2955-2964 (2006).
51. Gohla, A., Offermanns, S., Wilkie, T.M., and Schultz, G. Differential involvement of Ga12 and Ga13 in receptor-mediated stress fiber formation. J. Biol. Chem. 274, 17901-17907 (1999).
52. McLaughlin, J.N., Shen, L., Holinstat, M., Brooks, J.D., Dibenedetto, E., and Hamm, H.E. Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1. J. Biol. Chem. 280, 25048-25059 (2005).
53. Riobo, N.A. and Manning, D.R. Receptors coupled to heterotrimeric G proteins of the G12 family. Trends Pharmacol. Sci. 26, 146-154 (2005).
54. Lee, H.Y., Chung, J.W., Youn, S.W. 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. 100, 372-380 (2007).
55. Xie, D., Yin, D., Tong, X. et al. Cyr61 is overexpressed in gliomas and involved in integrin-linked kinase-mediated Akt and beta-catenin-TCF/Lef signaling pathways. Cancer Res. 64, 1987-1996 (2004).
56. Menendez, J.A., Vellon, L., Mehmi, I., Teng, P.K., Griggs, D.W., and Lupu, R. A novel CYR61-triggered 'CYR61-alphavbeta3 integrin loop' regulates breast cancer cell survival and chemosensitivity through activation of ERK1/ERK2 MAPK signaling pathway. Oncogene 24, 761-779 (2005).
57. Chen, C.C., Chen, N., and Lau, L.F. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J. Biol. Chem. 276, 10443-10452 (2001).
58. Lin, B.R., Chang, C.C., Chen, L.R. et al. Cysteine-rich 61 (CCN1) enhances chemotactic migration, transendothelial cell migration, and intravasation by concomitantly up-regulating chemokine receptor 1 and 2. Mol. Cancer Res. 5, 1111-1123 (2007).
59. Lin, M.T., Chang, C.C., Chen, S.T. et al. Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation. J. Biol. Chem. 279, 24015-24023 (2004).
60. Chen, C.C., Mo, F.E., and Lau, L.F. The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts. J. Biol. Chem. 276, 47329-47337 (2001).
61. Zhou, D., Herrick, D.J., Rosenbloom, J., and Chaqour, B. Cyr61 mediates the expression of VEGF, alphav-integrin, and alpha-actin genes through cytoskeletally based mechanotransduction mechanisms in bladder smooth muscle cells. J. Appl. Physiol. 98, 2344-2354 (2005).
62. Boire, A., Covic, L., Agarwal, A., Jacques, S., Sherifi, S., and Kuliopulos, A. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 120, 303-313 (2005).
63. Chien, W., Kumagai, T., Miller, C.W. et al. Cyr61 suppresses growth of human endometrial cancer cells. J. Biol. Chem. 279, 53087-53096 (2004).
64. Todorovic, V., Chen, C.C., Hay, N., and Lau, L.F. The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts. J. Cell Biol. 171, 559-568 (2005).
65. Matsumae, H., Yoshida, Y., Ono, K. et al. CCN1 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model. Arterioscler. Thromb. Vasc. Biol. 28, 1077-1083 (2008).
66. Seasholtz, T.M. and Brown, J.H. Rho signaling in vascular diseases. Mol. Interv. 4, 348-357 (2004).
67. Tong, X., Xie, D., O'Kelly, J., Miller, C.W., Muller-Tidow, C., and Koeffler, H.P. Cyr61, a member of CCN family, is a tumor suppressor in nonsmall cell lung cancer. J. Biol. Chem. 276, 47709-47714 (2001).
68. Tong, X., O'Kelly, J., Xie, D. et al. Cyr61 suppresses the growth of nonsmall-cell lung cancer cells via the beta-catenin-c-myc-p53 pathway. Oncogene 23, 4847-4855 (2004).
69. Chen, C.C., Young, J.L., Monzon, R.I., Chen, N., Todorovic, V., and Lau, L.F. Cytotoxicity of TNFalpha is regulated by integrin-mediated matrix signaling. EMBO J. 26, 1257-1267 (2007).
70. Jedsadayanmata, A., Chen, C.C., Kireeva, M.L., Lau, L.F., and Lam, S.C. Activation-dependent adhesion of human platelets to Cyr61 and Fisp12/mouse connective tissue growth factor is mediated through integrin alpha(IIb)beta(3). J. Biol. Chem. 274, 24321-24327 (1999).
71. Citro, S., Radeff-Huang, J., Kelley, G.G., Smrcka, A. and Brown, J.H. Phospholipase Ce is a nexus for Rho and Rap-mediated GPCR induced astrocyte proliferation. Proc. Natl. Acad. Sci. USA 104, 15543-15548 (2007). A novel form of phospholipase C, PLC epsilon, is directly activated by small G proteins including RhoA. Here we demonstrate, using PLC epsilon knockout mice, that PLC epsilon is the predominant phosholipase isoform used for thrombin, S1P, and LPA signaling in astrocytes. We further demonstrate additional functions for this PLC in mediating sustained MAP kinase activation and thrombin-induced proliferation.