Cell shape, adhesion, and motility are affected by Ca-regulated pathways, which depend on Ca-binding proteins. One such protein is calreticulin, a ubiquitous and major Ca-binding protein, resident in the ER of eukaryotic cells. In the lumen of the ER, calreticulin is a lectin-like chaperone, sharing this function with an ER-membrane protein, calnexin. Calreticulin also functions as an ER-lumenal Ca store and plays a central role in intracellular Ca homeostasis, including the regulation of store-operated Ca influx via plasma membrane and ER Ca channels. Calreticulin also affects processes outside of the ER; most notably, it modulates expression of several genes, some of them adhesion related, such as vinculin and fibronectin. Curiously, changes in the expression level of calreticulin strongly affect tyrosine phosphorylation of cellular proteins, which is known to affect many adhesion-related functions. Consequently, calreticulin affects cell adhesion via the regulation of expression of proteins important in adhesion, as well as via its effects on intracellular signalling pathways. One of the proteins differentially phosphorylated in a calreticulin-dependent manner is beta-catenin, a structural component of cadherin-mediated adhesion complexes and a part of the Wnt signalling pathway. We suggest that the observed changes in cell adhesiveness may be due to calreticulin's influence on a signalling pathway from the ER, which includes the beta-catenin/ vinculin protein system. Differential expression of calreticulin may affect the phosphorylation status of beta-catenin by either inhibition of specific phosphotyrosine kinase(s) or activation of phosphotyrosine phosphatase(s). This is likely to affect the balance between complexed and free beta-catenin and impinge further down on the Wnt signalling. At present, the mechanism by which calreticulin affects gene expression can only be speculated upon, but our data indicate that calreticulin, via its effects on Ca release from the ER, may indirectly control the expression of several genes by interfering with calcineurin activity and the ability of the transcription factor, NFAT-3, to translocate to the nucleus. The activation of calcineurin depends on the sustained release of Ca from ER stores, which is dependent on calreticulin.
In summary, we propose that calreticulin may be a centrally located connector molecule in a signalling network in the lumen of the ER. Calreticulin is uniquely endowed for such regulation because it is a multifunctional protein that interacts with several other ER proteins in a Ca-dependent manner, suggesting that it may function as a signalling "toggle switch". We therefore hypothesize that calreticulin regulates gene expression by participating in an "ER-to-nucleus" signalling pathway, which parallels an "ER-to-cell surface" pathway based upon post-translational events.
calreticulin; calcium; adhesion; extracellular matrix
Adams JC: Cell-matrix contact structures. Cell Mol Life Sci 58:371-392, 2001.
Ai Z, Fischer A, Spray DC, Brown AM, Fishman GI: Wnt-1 regulation of connexin43 in cardiac myocytes. J Clin Invest 105:161-171, 2000.
Angers-Loustau A, Cote JF, Tremblay ML: Roles of protein tyrosine phosphatases in cell migration and adhesion. Biochem Cell Biol 77:493-505, 1999.
Baksh S, Burns K, Andrin C, Michalak M: Interaction of calreticulin with protein disulfide isomerase. J Biol Chem 270:31338-31344, 1995.
Barth AI, Nathke IS, Nelson WJ: Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol 9:683-690, 1997.
Bastianutto C, Clementi E, Codazzi F, Podini P, De Giorgi F, Rizzuto R, Meldolesi J, Pozzan T: Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. J Cell Biol 130:847-855, 1995.
Beckerle MC, Burridge K, DeMartino GN, Croall DE: Colocalization of calcium-dependent protease II and one of its substrates at sites of cell adhesion. Cell 51:569-577, 1987.
Behrens J: Cadherins and catenins: Role in signal transduction and tumor progression. Cancer Metastasis Rev 18:15-30, 1999.
Ben-Ze'ev A: Cytoskeletal and adhesion proteins as tumor suppressors. Curr Opin Cell Biol 9:99-108, 1997.
Bereiter-Hahn J, Fox CH, Thorell B: Quantitative reflection contrast microscopy of living cells. J Cell Biol 82:767-779, 1979.
Burns K, Atkinson EA, Bleackley RC, Michalak M: Calreticulin: From Ca2+ binding to control of gene expression. Trends Cell Biol 4:152-154, 1994a.
Burns K, Duggan B, Atkinson EA, Famulski KS, Nemer M, Bleackley RC, Michalak M: Modulation of gene expression by calreticulin binding to the glucocorticoid receptor. Nature 367:476-480, 1994b.
Burridge K, Chrzanowska-Wodnicka M: Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol 12:463-518, 1996.
Burridge K, Chrzanowska-Wodnicka M, Zhong CL: Focal adhesion assembly. Trends Cell Biol 7:342-347, 1997.
Burridge K, Fath K, Kelly T, Nuckolls G, Turner C: Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol 4:487-525, 1988.
Burridge K, Turner CE, Romer LH: Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: A role in cytoskeletal assembly. J Cell Biol 119:893-903, 1992.
Camacho P, Lechleiter JD: Calreticulin inhibits repetitive intracellular Ca2+ waves. Cell 82:765-771, 1995.
Chapman R, Sidrauski C, Walter P: Intracellular signaling from the endoplasmic reticulum to the nucleus. Annu Rev Cell Dev Biol 14:459-485, 1998.
Chen RH, Ding WV, McCormick F: Wnt signaling to beta-catenin involves two interactive components - Glycogen synthase kinase-3beta inhibition and activation of protein kinase C. J Biol Chem 275:17894-17899, 2000.
Chen W-T: Transmembrane interactions at cell adhesion and invasion sites. Cell Differ Dev 32:329-336, 1990.
Chen W-T, Greve JM, Gottlieb DI, Singer SJ: Immunocytochemical localization of 140 kD cell adhesion molecules in cultured chicken fibroblasts, and in chicken smooth muscle and intestinal epithelial tissues. J Histochem Cytochem 33:576-586, 1985a.
Chen W-T, Hasegawa E, Hasegawa T, Weinstock C, Yamada KM: Development of cell surface linkage complexes in cultured fibroblasts. J Cell Biol 100:1103-1114, 1985b.
Chen W-T, Singer SJ: Immunoelectron microscopic studies of the sites of cell-substratum and cell-cell contacts in cultured fibroblasts. J Cell Biol 95:205-222, 1982.
Christiansen JH, Goles EG, Wilkinson DG: Molecular control of neural crest formation, migration and differentiation. Curr Opin Cell Biol 12:719-724, 2000.
Coppolino M, Leung-Hagesteijn C, Dedhar S, Wilkins J: Inducible interaction of integrin alpha2beta1 with calreticulin - Dependence on the activation state of the integrin. J Biol Chem 270:23132-23138, 1995.
Coppolino MG, Dedhar S: Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation dephosphorylation events. Biochem J 340:41-50, 1999.
Coppolino MG, Woodside MJ, Demaurex N, Grinstein S, St-Arnaud R, Dedhar S: Calreticulin is essential for integrin-mediated calcium signalling and cell adhesion. Nature 386:843-847, 1997.
Crawford AW, Beckerle MC: Purification and characterization of zyxin, an 82,000-dalton component of adherens junctions. J Biol Chem 266:5847-5853, 1991.
Crawford AW, Michelsen JW, Beckerle MC: An interaction between zyxin and alpha-actinin. J Cell Biol 116:1381-1393, 1992.
Critchley DR: Focal adhesions - the cytoskeletal connection. Curr Opin Cell Biol 12:133-139, 2000.
Curtis ASG: The mechanism of adhesion of cells to glass. J Cell Biol 20:199-215, 1964.
Daniel JM, Reynolds AB: Tyrosine phosphorylation and cadherin/catenin function. BioEssays 19:883-891, 1997.
Davis S, Lu ML, Lo SH, Lin S, Butler JA, Druker BJ, Roberts TM, An Q, Chen LB: Presence of an SH2 domain in the actin-binding protein tensin. Science 252:712-715, 1991.
Dean DC: Expression of the fibronectin gene. Am J Respir Cell Mol Biol 1:5-10, 1989.
Dedhar S: Novel functions for calreticulin: Interaction with integrins and modulation of gene expression. Trends Biochem Sci 19:269-271, 1994.
Dedhar S, Rennie PS, Shago M, Leung-Hagesteijn MC-Y, Yang H, Filmus J, Hawley RG, Bruchovsky N, Cheng H, Matusik RJ, Giguere V: Inhibition of nuclear hormone receptor activity by calreticulin. Nature 367:480-483, 1994.
Desai D, Michalak M, Singh NK, Niles RM: Inhibition of retinoic acid receptor function and retinoic acid- regulated gene expression in mouse melanoma cells by calreticulin - A potential pathway for cyclic AMP regulation of retinoid action. J Biol Chem 271:15153-15159, 1996.
Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI: Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 386:855-858, 1997.
Dolmetsch RE, Xu KL, Lewis RS: Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392:933-936, 1998.
Eastman Q, Grosschedl R: Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol 11:233-240, 1999.
Fadel MP, Dziak E, Lo CM, Ferrier J, Mesaeli N, Michalak M, Opas M: Calreticulin affects focal contact-dependent but not close contact-dependent cell-substratum adhesion. J Biol Chem 274:15085-15094, 1999.
Fadel MP, Szewczenko-Pawlikowski M, Leclerc P, Dziak E, Symonds JM, Blaschuk O, Michalak M, Opas M: Calreticulin affects beta-catenin associated pathways. J Biol Chem 276:27083-27089, 2001.
Fasolato C, Pizzo P, Pozzan T: Delayed activation of the store-operated calcium current induced by calreticulin overexpression in RBL-1 cells. Mol Biol Cell 9:1513-1522, 1998.
Fliegel L, Burns K, MacLennan DH, Reithmeier RAF, Michalak M: Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum. J Biol Chem 264:21522-21528, 1989a.
Fliegel L, Burns K, Opas M, Michalak M: The high-affinity calcium binding protein of sarcoplasmic reticulum. Tissue distribution, and homology with calregulin. Biochim Biophys Acta 982:1-8, 1989b.
Fukata M, Nakagawa M, Kuroda S, Kaibuchi K: Cell adhesion and Rho small GTPases. J Cell Sci 112:4491-4500, 1999.
Geiger B, Bershadsky A: Assembly and mechanosensory function of focal contacts. Curr Opin Cell Biol 13:584-592, 2001.
Geiger B, Bershadsky A, Pankov R, Yamada KM: Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2:793-805, 2001.
Gingell D: The interpretation of interference-reflection images of spread cells: Significant contributions from thin peripheral cytoplasm. J Cell Sci 49:237-247, 1981.
Gingell D, Todd I: Interference reflection microscopy. A quantitative theory for image interpretation and its application to cell-substratum separation measurement. Biophys J 26:507-526, 1979.
Guan J-L, Shalloway D: Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 358:690-692, 1992.
Guan J-L, Trevithick JE, Hynes RO: Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein. Cell Regul 2:951-964, 1991.
Hanks SK, Calalb MB, Harper MC, Patel SK: Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci USA 89:8487-8491, 1992.
Hanks SK, Polte TR: Signaling through focal adhesion kinase. BioEssays 19:137-145, 1997.
Hazan RB, Kang L, Roe S, Borgen PI, Rimm DL: Vinculin is associated with the E-cadherin adhesion complex. J Biol Chem 272:32448-32453, 1997.
Hazan RB, Norton L: The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton. J Biol Chem 273:9078-9084, 1998.
Heath JP, Dunn GA: Cell to substratum contacts of chick fibroblasts and their relation to the microfilament system. A correlated interference-reflexion and high-voltage electron-microscope study. J Cell Sci 29:197-212, 1978.
Hecht A, Kemler R: Curbing the nuclear activities of beta-catenin. Control over Wnt target gene expression. EMBO Rep 1:24-28, 2000.
Helenius A, Trombetta ES, Hebert DN, Simons JF: Calnexin, calreticulin and the folding of glycoproteins. Trends Cell Biol 7:193-200, 1997.
Herman B, Roe MW, Harris C, Wray B, Clemmons D: Platelet-derived growth factor-induced alterations in vinculin distribution in porcine vascular smooth muscle cells. Cell Motil Cytoskeleton 8:91-105, 1987.
Holaska JM, Black BE, Love DC, Hanover JA, Leszyk J, Paschal BM: Calreticulin is a receptor for nuclear export. J Cell Biol 152:127-140, 2001.
Hunter T: Protein modification: phosphorylation on tyrosine residues. Curr Opin Cell Biol 1:1168-1181, 1989.
Huttenlocher A, Lakonishok M, Kinder M, Wu S, Truong T, Knudsen KA, Horwitz AF: Integrin and cadherin synergy regulates contact inhibition of migration and motile activity. J Cell Biol 141:515-526, 1998.
Hyatt SL, Klauck T, Jaken S: Protein kinase C is localized in focal contacts of normal but not transformed fibroblasts. Mol Carcinog 3:45-53, 1990.
Hynes RO: Integrins: Versatility, modulation, and signaling in cell adhesion. Cell 69:11-25, 1992.
Izzard CS, Lochner LR: Cell-to-substrate contacts in living fibroblasts: an interference reflexion study with an evaluation of the technique. J Cell Sci 21:129-159, 1976.
Jaken S, Leach K, Klauck T: Association of type 3 protein kinase C with focal contacts in rat embryo fibroblasts. J Cell Biol 109:697-704, 1989.
Jockusch BM, Bubeck P, Giehl K, Kroemker M, Moscher J, Rothkegel M, Rudiger M, Schluter K, Stanke G, Winkler J: The molecular architecture of focal adhesions. Annu Rev Cell Dev Biol 11:379-416, 1995.
John LM, Lechleiter JD, Camacho P: Differential modulation of SERCA2 isoforms by calreticulin. J Cell Biol 142:963-973, 1998.
Johnson S, Michalak M, Opas M, Eggleton P: The ins and outs of calreticulin: from the ER lumen to the extracellular space. Trends Cell Biol 11:122-129, 2001.
Jouaville LS, Ichas F, Holmuhamedov EL, Camacho P, Lechleiter JD: Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes. Nature 377:438-441, 1995.
Juliano RL, Haskill S: Signal transduction from the extracellular matrix. J Cell Biol 120:577-585, 1993.
Kalcheim C: Mechanisms of early neural crest development: From cell specification to migration. Int Rev Cytol 200:143-196, 2000.
Kaufman RJ: Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13:1211-1233, 1999.
Kellie S: Cellular transformation, tyrosine kinase oncogenes, and the cellular adhesion plaque. BioEssays 8:25-30, 1988.
Kellie S, Horvath AR, Elmore MA: Cytoskeletal targets for oncogenic tyrosine kinases. J Cell Sci 99:207-211, 1991.
Knee R, Ahsan I, Mesaeli N, Kaufman RJ, Michalak M: Compromised calnexin function in calreticulin-deficient cells. Biochem Biophys Res Commun 304:661-666, 2003.
Kolega J, Shure MS, Chen W-T, Young ND: Rapid cellular translocation is related to close contacts formed between various cultured cells and their substrata. J Cell Sci 54:23-34, 1982.
Kornberg L, Earp HS, Parsons JT, Schaller M, Juliano RL: Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase. J Biol Chem 267:23439-23442, 1992.
Kornberg L, Juliano RL: Signal transduction from the extracellular matrix: The integrin-tyrosine kinase connection. Trends Pharmacol Sci 13:93-95, 1992.
Kornberg LJ, Earp HS, Turner CE, Prockop C, Juliano RL: Signal transduction by integrins: Increased protein tyrosine phosphorylation caused by clustering of beta1 integrins. Proc Natl Acad Sci USA 88:8392-8396, 1991.
Kornblihtt AR, Pesce CG, Alonso CR, Cramer P, Srebrow A, Werbajh S, Muro AF: The fibronectin gene as a model for splicing and transcription studies. FASEB J 10:248-257, 1996.
Kuhl M, Sheldahl LC, Park M, Miller JR, Moon RT: The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 16:279-283, 2000.
Laudet V, Hanni C, Coll J, Catzeflis F, Stehelin D: Evolution of the nuclear receptor gene superfamily. EMBO J 11:1003-1013, 1991.
Leung-Hagesteijn C-Y, Milankov K, Michalak M, Wilkins J, Dedhar S: Cell attachment to extracellular matrix substrates is inhibited upon downregulation of expression of calreticulin, an intracellular integrin alpha-subunit-binding protein. J Cell Sci 107:589-600, 1994.
Li L, Okura M, Imamoto A: Focal adhesions require catalytic activity of SRC family kinases to mediate integrin-matrix adhesion. Mol Cell Biol 22:1203-1217, 2002.
Li WH, Llopis J, Whitney M, Zlokarnik G, Tsien RY: Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature 392:936-941, 1998.
Liebl EC, Martin GS: Intracellular targeting of pp60src expression: localization of v-src to adhesion plaques is sufficient to transform chicken embryo fibroblasts. Oncogene 7:2417-2428, 1992.
Maher PA, Pasquale EB, Wang JY, Singer SJ: Phosphotyrosine-containing proteins are concentrated in focal adhesions and intercellular junctions in normal cells. Proc Natl Acad Sci USA 82:6576-6580, 1985.
Martini R, Schachner M: Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and MAG) and their shared carbohydrate epitope and myelin basic protein in developing sciatic nerve. J Cell Biol 103:2439-2448, 1986.
McMillan A, Gething M-J, Sambrook J: Intercompartmental signaling. Curr. Opinion Biotech 6:540-545, 1994.
McNamee HP, Ingber DE, Schwartz MA: Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown. J Cell Biol 121:673-678, 1993.
Meigs JB, Wang Y-L: Reorganization of alpha-actinin and vinculin induced by a phorbol ester in living cells. J Cell Biol 102:1430-1438, 1986.
Mery L, Mesaeli N, Michalak M, Opas M, Lew DP, Krause K-H: Overexpression of calreticulin increases intracellular Ca2+-storage and decreases store-operated Ca2+ influx. J Biol Chem 271:9332-9339, 1996.
Mesaeli N, Nakamura K, Zvaritch E, Dickie P, Dziak E, Krause KH, Opas M, MacLennan DH, Michalak M: Calreticulin is essential for cardiac development. J Cell Biol 144:857-868, 1999.
Michalak M, Burns K, Mesaeli N, Andrin C, Busaan JL, Jass GH, Opas M: Endoplasmic reticulum form of calreticulin modulates glucocorticoid-sensitive gene expression. J Biol Chem 271:29436-29445, 1996.
Michalak M, Corbett EF, Mesaeli N, Nakamura K, Opas M: Calreticulin: one protein, one gene and many functions. Biochem J 344:281-292, 1999.
Miller JR, Hocking AM, Brown JD, Moon RT: Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways. Oncogene 18:7860-7872, 1999.
Nakamura K, Zuppini A, Arnaudeau S, Lynch J, Ahsan I, Krause R, Papp S, De Smedt H, Parys JB, Muller-Esterl W, Lew DP, Krause KH, Demaurex N, Opas M, Michalak M: Functional specialization of calreticulin domains. J Cell Biol 154:961-972, 2001.
Ohashi T, Kiehart DP, Erickson HP: Dual labeling of the fibronectin matrix and actin cytoskeleton with green fluorescent protein variants. J Cell Sci 115:1221-1229, 2002.
Opas M: Adhesion of cells to protein carpets: do cells' feet have to be black? Cell Motil Cytoskelet 11:178-181, 1988.
Opas M, Szewczenko-Pawlikowski M, Jass GK, Mesaeli N, Michalak M: Calreticulin modulates cell adhesiveness via regulation of vinculin expression. J Cell Biol 135:1913-1923, 1996.
Otey CA: pp125FAK in the focal adhesion. Int Rev Cytol 167:161-183, 1996.
Pahl HL, Baeuerle PA: Endoplasmic reticulum-induced signal transduction and gene expression. Trends Cell Biol 7:50-55, 1997a.
Pahl HL, Baeuerle PA: The ER-overload response: Activation of NF-kappaB. Trends Biochem Sci 22:63-67, 1997b.
Pankov R, Cukierman E, Katz BZ, Matsumoto K, Lin DC, Lin S, Hahn C, Yamada KM: Integrin dynamics and matrix assembly: tensin-dependent translocation of alpha5beta1 integrins promotes early fibronectin fibrillogenesis. J Cell Biol 148:1075-1090, 2000.
Parsons JT: Integrin-mediated signalling: regulation by protein tyrosine kinases and small GTP-binding proteins. Curr Opin Cell Biol 8:146-152, 1996.
Peifer M, Polakis P: Cancer-Wnt signaling in oncogenesis and embryogenesis - a look outside the nucleus. Science 287:1606-1609, 2000.
Piedra J, Martinez D, Castano J, Miravet S, Dunach M, De Herreros AG: Regulation of beta-catenin structure and activity by tyrosine phosphorylation. J Biol Chem 276:20436-20443, 2001.
Rao A, Luo C, Hogan PG: Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 15:707-747, 1997.
Rauch F, Prud'homme J, Arabian A, Dedhar S, St Arnaud R: Heart, brain, and body wall defects in mice lacking calreticulin. Exp Cell Res 256:105-111, 2000.
Ridley AJ: Rho GTPases and cell migration. J Cell Sci 114:2713-2722, 2001.
Rohrschneider L, Rosok M, Shriver K: Mechanism of transformation by rous sarcoma virus: events within adhesion plaques. Cold Spring Harbor Symp Quant Biol 46:953-968, 1982.
Rojiani MV, Finlay BB, Gray V, Dedhar S: In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits. Biochemistry 30:9859-9866, 1991.
Rottner K, Hall A, Small JV: Interplay between Rac and Rho in the control of substrate contact dynamics. Curr Biol 9:640-648, 1999.
Sadler I, Crawford AW, Michelsen JW, Beckerle MC: Zyxin and cCRP: two interactive LIM domain proteins associated with the cytoskeleton. J Cell Biol 119:1573-1587, 1992.
Sastry SK, Burridge K: Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp Cell Res 261:25-36, 2000.
Schaller MD: Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta Mol Cell Res 1540:1-21, 2001.
Schwartz MA, Lechene C, Ingber DE: Insoluble fibronectin activates the Na/H antiporter by clustering and immobilizing integrin alpha5beta1, independent of cell shape. Proc Natl Acad Sci USA 88:7849-7853, 1991.
Schwartz MA, Shattil SJ: Signaling networks linking integrins and Rho family GTPases. Trends Biochem Sci 25:388-391, 2000.
Schwarzbauer JE: Fibronectin: from gene to protein. Curr Opin Cell Biol 3:786-791, 1991.
Sefton BM, Hunter T: Vinculin: a cytoskeletal target of the transforming protein of Rous Sarcoma Virus. Cell 24:165-174, 1981.
Seidensticker MJ, Behrens J: Biochemical interactions in the wnt pathway. Biochim Biophys Acta 1495:168-182, 2000.
Senger DR, Destree AT, Hynes RO: Complex regulation of fibronectin synthesis by cells in culture. Am J Physiol 245:C144-C150, 1983.
Shago M, Flock G, Hagesteijn CYL et al.: Modulation of the retinoic acid and retinoid X receptor signaling pathways in P19 embryonal carcinoma cells by calreticulin. Exp Cell Res 230:50-60, 1997.
Shibasaki F, Price ER, Milan D, McKeon F: Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4. Nature 382:370-373, 1996.
Shriver K, Rohrschneider L: Organization of pp60src and selected cytoskeletal proteins within adhesion plaques and junctions of Rous Sarcoma Virus-transformed rat cells. J Cell Biol 89:525-535, 1981.
Singer II: The fibronexus: A transmembrane association of fibronectin- containing fibers and bundles of 5nm microfilaments in hamster and human fibroblasts. Cell 16: 675-685, 1979.
Singer II: Fibronexus formation is an early event during fibronectin- induced restoration of more normal morphology and substrate adhesion patterns in transformed hamster fibroblasts. J Cell Sci 56:1-20, 1982.
St-Arnaud R, Prud'homme J, Leung-Hagesteijn C, Dedhar S: Constitutive expression of calreticulin in osteoblasts inhibits mineralization. J Cell Biol 131:1351-1359, 1995.
Turner CE, Glenney JR Jr., Burridge K: Paxillin: a new vinculin-binding protein present in focal adhesions. J Cell Bio. 111:1059-1068, 1990.
Turner CE, Pavalko FM, Burridge K: The role of phosphorylation and limited proteolytic cleavage of talin and vinculin in the disruption of focal adhesion integrity. J Biol Chem 264:11938-11944, 1989.
van der Heyden MA, Rook MB, Hermans MM, Rijksen G, Boonstra J, Defize LH, Destree OH: Identification of connexin43 as a functional target for Wnt signalling. J Cell Sci 111:1741-1749, 1998.
Verschueren H: Interference reflection microscopy in cell biology: methodology and applications. J Cell Sci 75:279-301, 1985.
Volberg T, Geiger B, Dror R, Zick Y: Modulation of intercellular adherens-type junctions and tyrosine phosphorylation of their components in RSV-transformed cultured chick lens cells. Cell Regul 2:105-120, 1991.
Volberg,T, Zick Y, Dror R, Sabanay I, Gilon C, Levitzki A, Geiger B: The effect of tyrosine-specific protein phosphorylation on the assembly of adherens-type junctions. EMBO J 11:1733-1742, 1992.
Wakasaki H, Koya D, Schoen FJ, Jirousek MR, Ways DK, Hoit BD, Walsh RA, King GL: Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy. Proc Natl Acad Sci USA 94:9320-9325, 1997.
Wang Z, Tufts R, Haleem R, Cai X: Genes regulated by androgen in the rat ventral prostate. Proc Natl Acad Sci USA 94:12999-13004, 1997.
Wheeler DG, Horsford J, Michalak M, White JH, Hendy GN: Calreticulin inhibits vitamin D3 signal transduction. Nucl Acids Res 23:3268-3274, 1995.
Williams MJ, Hughes PE, O'Toole TE, Ginsberg MH: The inner world of cell adhesion: integrin cytoplasmic domains. Trends Cell Biol 4:109-112, 1994.
Woods A, Couchman JR: Protein kinase C involvement in focal adhesion formation. J Cell Sci 101:277-290, 1992.
Xu WM, Baribault H, Adamson ED: Vinculin knockout results in heart and brain defects during embryonic development. Development 125:327-337, 1998.
Yamada KM, Miyamoto S: Integrin transmembrane signaling and cytoskeletal control. Curr Opin Cell Biol 7:681-689, 1995.
Yuruker B, Niggli V: alpha-Actinin and vinculin in human neutrophils: Reorganization during adhesion and relation to the actin network. J Cell Sci 101:403-414, 1992.
Zamir E, Geiger B: Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 114:3583-3590, 2001.
Zamir E, Katz M, Posen Y, Erez N, Yamada KM, Katz BZ, Lin S, Lin DC, Bershadsky A, Kam Z, Geiger B: Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nat Cell Biol 2:191-196, 2000.
Zapun A, Darby NJ, Tessier DC, Michalak M, Bergeron JJM, Thomas DY: Enahanced catalysis of ribonuclease B folding by the interaction of calnexin or calreticulin with ERp57. J Biol Chem 273:6009-6012, 1998.
Zhou Y, Dziak E, Opas M: Adhesiveness and proliferation of epithelial cells are differentially modulated by activation and inhibition of protein kinase C in substratum-dependent manner. J Cell Physiol 155:14-26, 1993.
Castaneda-Patlan MC, Razo-Paredes R, Carrisoza-Gaytan R, Gonzalez-Mariscal L, Robles-Flores M: Protein kinase C is involved in the regulation of several calreticulin posttranslational modifications. Int J Biochem Cell Biol 42:120-131, 2010.
Papp S, Fadel MP, Michalak M, Opas M: Analysis of the suitability of calreticulin inducible HEK cells for adhesion studies: microscopical and biochemical comparisons. Mol Cell Bioch 307:237-248, 2008.
Szabo E, Papp S, Opas M: Differential calreticulin affects focal contacts via the Calmodulin/CaMK II pathway. J Cell Physiol 213:269-277, 2007.
Papp S, Fadel MP, Opas M: Dissecting focal adhesions in cells differentially expressing calreticulin: a microscopy study. Biol Cell 99:389-402, 2007.
Chen Y, Lin P, Qiu SM, Peng XX, Looi K, Farquhar MG, Zhang JY: Autoantibodies to Ca2+ binding protein Calnuc is a potential marker in colon cancer detection. Int J Oncol 30:1137-1144, 2007.
Opas M, Fadel MP: Partial reversal of transformed fusiform phenotype by overexpression of calreticulin Cell Mol Biol Lett 12:294-307, 2007.
Lozyk MD, Papp S, Zhang XC, Nakamura K, Michalak M, Opas M: Ultrastructural analysis of development of myocardium in calreticulin-deficient mice. BMC Develop Biol 6:54, 2006.
Szabo E, Papp S, Opas M: Calreticulin and cellular adhesion/migration-specific signalling pathways. In Berger J (ed), Advances in Cell and Mollecular Biology. 6th Cells Conference 2005, Oct 24-26, 2005 Univ S Bohemia, Ceske Budejovice, Czech Republic, pp. 129-146, 2005.