Skip to main content
Download PDF
  • Research Article
  • Published:

Calreticulin affects cell adhesiveness through differential phosphorylation of insulin receptor substrate-1

Cellular & Molecular Biology Letters volume 19, pages 77–97 (2014)Cite this article

Abstract

Cellular adhesion to the underlying substratum is regulated through numerous signaling pathways. It has been suggested that insulin receptor substrate 1 (IRS-1) is involved in some of these pathways, via association with and activation of transmembrane integrins. Calreticulin, as an important endoplasmic reticulum-resident, calcium-binding protein with a chaperone function, plays an obvious role in proteomic expression. Our previous work showed that calreticulin mediates cell adhesion not only by affecting protein expression but also by affecting the state of regulatory protein phosphorylation, such as that of c-src. Here, we demonstrate that calreticulin affects the abundance of IRS-1 such that the absence of calreticulin is paralleled by a decrease in IRS-1 levels and the unregulated overexpression of calreticulin is accompanied by an increase in IRS-1 levels. These changes in the abundance of calreticulin and IRS-1 are accompanied by changes in cell-substratum adhesiveness and phosphorylation, such that increases in the expression of calreticulin and IRS-1 are paralleled by an increase in focal contact-based cellsubstratum adhesiveness, and a decrease in the expression of these proteins brings about a decrease in cell-substratum adhesiveness. Wild type and calreticulin-null mouse embryonic fibroblasts (MEFs) were cultured and the IRS-1 isoform profile was assessed. Differences in morphology and motility were also quantified. While no substantial differences in the speed of locomotion were found, the directionality of cell movement was greatly promoted by the presence of calreticulin. Calreticulin expression was also found to have a dramatic effect on the phosphorylation state of serine 636 of IRS-1, such that phosphorylation of IRS-1 on serine 636 increased radically in the absence of calreticulin. Most importantly, treatment of cells with the RhoA/ROCK inhibitor, Y-27632, which among its many effects also inhibited serine 636 phosphorylation of IRS-1, had profound effects on cell-substratum adhesion, in that it suppressed focal contacts, induced extensive close contacts, and increased the strength of adhesion. The latter effect, while counterintuitive, can be explained by the close contacts comprising labile bonds but in large numbers. In addition, the lability of bonds in close contacts would permit fast locomotion. An interesting and novel finding is that Y-27632 treatment of MEFs releases them from contact inhibition of locomotion, as evidenced by the invasion of a cell’s underside by the thin lamellae and filopodia of a cell in close apposition.

Abbreviations

CRT:

calreticulin

ECM:

extracellular matrix

ER:

endoplasmic reticulum

FAK:

focal adhesion kinase

IRS-1:

insulin receptor substrate 1

KO:

knockout

MEF:

mouse embryonic fibroblast

ROCK:

Rho-associated kinase

WT:

wild type

References

  1. Burridge, K., Fath, K., Kelly, T., Nuckolls, G. and Turner, C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu. Rev. Cell Biol. 4 (1988) 487–525.

    Article  PubMed  CAS  Google Scholar 

  2. McClay, D.R. and Ettensohn, C.A. Cell adhesion in morphogernesis. Annu. Rev. Cell Biol. 3 (1987) 319–345.

    Article  PubMed  CAS  Google Scholar 

  3. Strohmeier, R. and Bereiter-Hahn, J. Control of cell shape and locomotion by external calcium. Exp. Cell Res. 154 (1984) 412–420.

    Article  PubMed  CAS  Google Scholar 

  4. Hinrichsen, R.D. Calcium and calmodulin in the control of cellular behavior and motility. Biochim. Biophys. Acta 1155 (1993) 277–293.

    PubMed  CAS  Google Scholar 

  5. Huttenlocher, A., Palecek, S.P., Lu, Q., Zhang, W.L., Mellgren, R.L., Lauffenburger, D.A., Ginsberg, M.H. and Horwitz, A.F. Regulation of cell migration by the calcium-dependent protease calpain. J. Biol. Chem. 272 (1997) 32719–32722.

    Article  PubMed  CAS  Google Scholar 

  6. Bolsover, S.R. Calcium signaling in growth cone migration. Cell Calcium 37 (2005) 395–402.

    Article  PubMed  CAS  Google Scholar 

  7. Bedard, K., Szabo, E., Michalak, M. and Opas, M. Cellular functions of endoplasmic reticulum chaperones calreticulin, calnexin, and ERp57. Int. Rev. Cytol. 245 (2005) 91–121.

    Article  PubMed  CAS  Google Scholar 

  8. Villagomez, M., Szabo, E., Podchenko, A., Feng, T., Papp, S. and Opas, M. Calreticulin and focal contact-dependent adhesion. Biochem. Cell Biol. 87 (2009) 545–556.

    Article  PubMed  CAS  Google Scholar 

  9. Geiger, B., Volk, T. and Volberg, T. Molecular heterogeneity of adherens junctions. J. Cell Biol. 101 (1985) 1523–1531.

    Article  PubMed  CAS  Google Scholar 

  10. Opas, M., Szewczenko-Pawlikowski, M., Jass, G.K., Mesaeli, N. and Michalak, M. Calreticulin modulates cell adhesiveness via regulation of vinculin expression. J. Cell Biol. 135 (1996) 1913–1923.

    Article  PubMed  CAS  Google Scholar 

  11. Fadel, M.P., Dziak, E., Lo, C.M., Ferrier, J., Mesaeli, N., Michalak, M. and Opas, M. Calreticulin affects focal contact-dependent but not close contactdependent cell-substratum adhesion. J. Biol. Chem. 274 (1999) 15085–15094.

    Article  PubMed  CAS  Google Scholar 

  12. Opas, M. and Fadel, M.P. Partial reversal of transformed fusiform phenotype by overexpression of calreticulin. Cell. Mol. Biol. Lett. 12 (2007) 294–307.

    Article  PubMed  CAS  Google Scholar 

  13. Papp, S., Fadel, M.P. and Opas, M. Dissecting focal adhesions in cells differentially expressing calreticulin — a microscopical study. Biol. Cell 99 (2007) 389–402.

    Article  PubMed  CAS  Google Scholar 

  14. Papp, S., Fadel, M.P., Kim, H., McCulloch, C.A. and Opas, M. Calreticulin affects fibronectin-based cell-substratum adhesion via the regulation of c-src activity. J. Biol. Chem. 282 (2007) 16585–16598.

    Article  PubMed  CAS  Google Scholar 

  15. Szabo, E., Papp, S. and Opas, M. Differential calreticulin expression affects focal contacts via the calmodulin/Camk II pathway. J. Cell. Physiol. 213 (2007) 269–277.

    Article  PubMed  CAS  Google Scholar 

  16. Burridge, K. and Chrzanowska-Wodnicka, M. Focal adhesions, contractility, and signaling. Annu. Rev. Cell Dev. Biol. 12 (1996) 463–518.

    Article  PubMed  CAS  Google Scholar 

  17. Burridge, K., Chrzanowska-Wodnicka, M. and Zhong, C.L. Focal adhesion assembly. Trends Cell Biol. 7 (1997) 342–347.

    Article  PubMed  CAS  Google Scholar 

  18. Jockusch, B.M., Bubeck, P., Giehl, K., Kroemker, M., Moscher, J., Rothkegel, M., Rüdiger, M., Schlüter, K., Stanke, G. and Winkler, J. The molecular architecture of focal adhesions. Annu. Rev. Cell Dev. Biol. 11 (1995) 379–416.

    Article  PubMed  CAS  Google Scholar 

  19. Vuori, K. and Ruoslahti, E. Association of insulin receptor substrate-1 with integrins. Science 266 (1994) 1576–1578.

    Article  PubMed  CAS  Google Scholar 

  20. Goel, H.L., Fornaro, M., Moro, L., Teider, N., Rhim, J.S., King, M. and Languino, L.R. Selective modulation of type 1 insulin-like growth factor receptor signaling and functions by beta1 integrins. J. Cell Biol. 166 (2004) 407–418.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Lebrun, P., Mothe-Satney, I., Delahaye, L., Van Obberghen, E. and Baron, V. Insulin receptor substrate-1 as a signaling molecule for focal adhesion kinase pp125(FAK) and pp60(src). J. Biol. Chem. 273 (1998) 32244–32253.

    Article  PubMed  CAS  Google Scholar 

  22. Lebrun, P., Baron, V., Hauck, C.R., Schlaepfer, D.D. and Van Obberghen, E. Cell adhesion and focal adhesion kinase regulate insulin receptor substrate-1 expression. J. Biol. Chem. 275 (2000) 38371–38377.

    Article  PubMed  CAS  Google Scholar 

  23. El Annabi, S., Gautier, N. and Baron, V. Focal adhesion kinase and Src mediate integrin regulation of insulin receptor phosphorylation. FEBS Lett. 507 (2001) 247–252.

    Article  PubMed  Google Scholar 

  24. Lee, Y.J., Hsu, T.C., Du, J.Y., Valentijn, A.J., Wu, T.Y., Cheng, C.F., Yang, Z. and Streuli, C.H. Extracellular matrix controls insulin signaling in mammary epithelial cells through the RhoA/Rok pathway. J. Cell. Physiol. 220 (2009) 476–484.

    Article  PubMed  CAS  Google Scholar 

  25. Nakamura, K., Bossy-Wetzel, E., Burns, K., Fadel, M.P., Lozyk, M., Goping, I.S., Opas, M., Bleackley, R.C., Green, D.R. and Michalak, M. Changes in endoplasmic reticulum luminal environment affect cell sensitivity to apoptosis. J. Cell Biol. 150 (2000) 731–740.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Nakamura, K., Zuppini, A., Arnaudeau, S., Lynch, J., Ahsan, I., Krause, R., Papp, S., De Smedt, H., Parys, J.B., Muller-Esterl, W., Lew, D.P., Krause, K.H., Demaurex, N., Opas, M. and Michalak, M. Functional specialization of calreticulin domains. J. Cell Biol. 154 (2001) 961–972.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Zigler, J.S., Jr., Lepe-Zuniga, J.L., Vistica, B. and Gery, I. Analysis of the cytotoxic effects of light-exposed HEPES-containing culture medium. In Vitro Cell Dev. Biol. 21 (1985) 282–287.

    Article  PubMed  CAS  Google Scholar 

  28. Menssen, H.D., Herlyn, M., Rodeck, U. and Koprowski, H. Rapid dissociation of adherent human tumor cells by ultrasound. J. Immunol. Methods 104 (1987) 1–6.

    Article  PubMed  CAS  Google Scholar 

  29. Szabo, E., Papp, S. and Opas, M. Calreticulin and cellular adhesion/migration-specific signaling pathways. J. Appl. Biomed. 4 (2006) 45–52.

    CAS  Google Scholar 

  30. Zamir, E. and Geiger, B. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114 (2001) 3583–3590.

    PubMed  CAS  Google Scholar 

  31. Critchley, D.R. and Gingras, A.R. Talin at glance. J. Cell Sci. 121 (2008) 1345–1347.

    Article  PubMed  CAS  Google Scholar 

  32. Geiger, B. and Yamada, K.M. Molecular architecture and function of matrix adhesions. Cold Spring Harb. Perspect. Biol. 3 (2011) a005033.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Reiss, K., Wang, J.Y., Romano, G., Tu, X., Peruzzi, F. and Baserga, R. Mechanisms of regulation of cell adhesion and motility by insulin receptor substrate-1 in prostate cancer cells. Oncogene 20 (2001) 490–500.

    Article  PubMed  CAS  Google Scholar 

  34. Sun, X.J. and Liu, F. Phosphorylation of IRS proteins Yin-Yang regulation of insulin signaling. Vitam. Horm. 80 (2009) 351–387.

    Article  PubMed  CAS  Google Scholar 

  35. Furukawa, N., Ongusaha, P., Jahng, W.J., Araki, K., Choi, C.S., Kim, H.J., Lee, Y.H., Kaibuchi, K., Kahn, B.B., Masuzaki, H., Kim, J.K., Lee, S.W. and Kim, Y.B. Role of Rho-kinase in regulation of insulin action and glucose homeostasis. Cell Metab. 2 (1997) 119–120.

    Article  CAS  Google Scholar 

  36. Begum, N., Sandu, O.A., Ito, M., Lohmann, S.M. and Smolenski, A. Active Rho kinase (ROK-alpha ) associates with insulin receptor substrate-1 and inhibits insulin signaling in vascular smooth muscle cells. J. Biol. Chem. 277 (2002) 6214–6222.

    Article  PubMed  CAS  Google Scholar 

  37. Farah, S., Agazie, Y., Ohan, N., Ngsee, J.K. and Liu, X.J. A rho-associated protein kinase, ROKalpha, binds insulin receptor substrate-1 and modulates insulin signaling. J. Biol. Chem. 273 (1998) 4740–4746.

    Article  PubMed  CAS  Google Scholar 

  38. Chrzanowska-Wodnicka, M. and Burridge, K. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J. Cell Biol. 133 (1996) 1403–1415.

    Article  PubMed  CAS  Google Scholar 

  39. Rottner, K., Hall, A. and Small, J.V. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 9 (1999) 640–648.

    Article  PubMed  CAS  Google Scholar 

  40. Narumiya, S., Ishizaki, T. and Uehata, M. Use and properties of ROCKspecific inhibitor Y-27632. Methods Enzymol. 325 (2000) 273–284.

    Article  PubMed  CAS  Google Scholar 

  41. Guilherme, A., Torres, K. and Czech, M.P. Cross-talk between insulin receptor and integrin à5á1 signaling pathways. J. Biol. Chem. 273 (1998) 22899–22903.

    Article  PubMed  CAS  Google Scholar 

  42. Papp, S., Szabo, E., Kim, H., McCulloch, C.A. and Opas, M. Kinasedependent adhesion to fibronectin: regulation by calreticulin. Exp. Cell Res. 314 (2008) 1313–1326.

    Article  PubMed  CAS  Google Scholar 

  43. Curtis, A.S.G. The mechanism of adhesion of cells to glass. A study by interference reflection microscopy. J. Cell Biol. 20 (1964) 199–215.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  44. Izzard, C.S. and Lochner, L.R. Cell-to-substrate contacts in living fibroblasts: an interference reflexion study with an evaluation of the technique. J. Cell Sci. 21 (1976) 129–159.

    PubMed  CAS  Google Scholar 

  45. Bereiter-Hahn, J., Fox, C.H. and Thorell, B. Quantitative reflection contrast microscopy of living cells. J. Cell Biol. 82 (1979) 767–779.

    Article  PubMed  CAS  Google Scholar 

  46. Gingell, D. and Todd, I. Interference reflection microscopy. A quantitative theory for image interpretation and its application to cell-substratum separation measurement. Biophys. J. 26 (1979) 507–526.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. Omelchenko, T., Vasiliev, J.M., Gelfand, I.M., Feder, H.H. and Bonder, E.M. Mechanisms of polarization of the shape of fibroblasts and epitheliocytes: Separation of the roles of microtubules and Rho-dependent actin-myosin contractility. Proc. Natl. Acad. Sci. USA 99 (2002) 10452–10457.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Worthylake, R.A. and Burridge, K. RhoA and ROCK promote migration by limiting membrane protrusions. J. Biol. Chem. 278 (2003) 13578–13584.

    Article  PubMed  CAS  Google Scholar 

  49. Vega, F.M., Fruhwirth, G., Ng, T. and Ridley, A.J. RhoA and RhoC have distinct roles in migration and invasion by acting through different targets. J. Cell Biol. 193 (2011) 655–665.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Opas, M. Adhesion of cells to protein carpets: do cells’ feet have to be black? Cell Motil. Cytoskeleton 11 (1988) 178–181.

    Article  PubMed  CAS  Google Scholar 

  51. Opas, M. and Kalnins, V.I. Microfilament distribution and adhesion patterns in cultured cells after glutaraldehyde-formaldehyde fixation. Eur. J. Cell Biol. 33 (1984) 60–65.

    PubMed  CAS  Google Scholar 

  52. Weber, I. Reflection interference contrast microscopy. Methods Enzymol. 361 (2003) 34–47.

    Article  PubMed  CAS  Google Scholar 

  53. Wang, J.Y., Gualco, E., Peruzzi, F., Sawaya, B.E., Passiatore, G., Marcinkiewicz, C., Staniszewska, I., Ferrante, P., Amini, S., Khalili, K. and Reiss, K. Interaction between serine phosphorylated IRS-1 and beta1-integrin affects the stability of neuronal processes. J. Neurosci. Res. 85 (2007) 2360–2373.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Wang, Q., Bilan, P.J. and Klip, A. Opposite effects of insulin on focal adhesion proteins in 3T3-L1 adipocytes and in cells overexpressing the insulin receptor. Mol. Biol. Cell 9 (1998) 3057–3069.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  55. Gail, M.H. and Boone, C.W. The locomotion of mouse fibroblasts in tissue culture. Biophys. J. 10 (1970) 980–993.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  56. Couchman, J.R. and Rees, D.A. Actomyosin organization for adhesion, spreading, growth and movement in chick fibroblasts. Cell Biol. Int. Rep. 3 (1979) 431–439.

    Article  PubMed  CAS  Google Scholar 

  57. Couchman, J.R. and Rees, D.A. The behaviour of fibroblasts migrating from chick heart explants: Changes in adhesion, locomotion and growth, and in the distribution of actomyosin and fibronectin. J. Cell Sci. 39 (1979) 149–165.

    PubMed  CAS  Google Scholar 

  58. Kolega, J., Shure, M.S., Chen, W.T. and Young, N.D. Rapid cellular translocation is related to close contacts formed between various cultured cells and their substrata. J. Cell Sci. 54 (1982) 23–34.

    PubMed  CAS  Google Scholar 

  59. Pouyssegur, J. and Pastan, I. The directionality of locomotion of mouse fibroblasts. Role of cell adhesiveness. Exp. Cell Res. 121 (1979) 373–382.

    Article  PubMed  CAS  Google Scholar 

  60. Rid, R., Schiefermeier, N., Grigoriev, I., Small, J.V. and Kaverina, I. The last but not the least: the origin and significance of trailing adhesions in fibroblastic cells. Cell Motil. Cytoskeleton 61 (2005) 161–171.

    Article  PubMed  Google Scholar 

  61. Abercrombie, M. and Dunn, G.A. Adhesions of fibroblasts to substratum during contact inhibition observed by interference reflection microscopy. Exp. Cell Res. 92 (1975) 57–62.

    Article  PubMed  CAS  Google Scholar 

  62. Heath, J.P. and Dunn, G.A. 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 (1978) 197–212.

    PubMed  CAS  Google Scholar 

  63. Wehland, J., Osborn, M. and Weber, K. Cell-to-substratum contacts in living cells: a direct correlation between interference-reflexion and indirect-immunofluorescence microscopy using antibodies against actin and alphaactinin. J. Cell Sci. 37 (1979) 257–273.

    PubMed  CAS  Google Scholar 

  64. Izzard, C.S. and Lochner, L.R. Formation of cell-to-substrate contacts during fibroblast motility: an interference-reflexion study. J. Cell Sci. 42 (1980) 81–116.

    PubMed  CAS  Google Scholar 

  65. Yates, J.R. and Izzard, C.S. Cell-to-substrate contacts in an adhesiondefective mutant of Balb/c3T3 cells. J. Cell Sci. 52 (1981) 183–196.

    PubMed  CAS  Google Scholar 

  66. Arthur, W.T. and Burridge, K. RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity. Mol. Biol. Cell 12 (2001) 2711–2720.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  67. Patla, I., Volberg, T., Elad, N., Hirschfeld-Warneken, V., Grashoff, C., Fassler, R., Spatz, J.P., Geiger, B. and Medalia, O. Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography. Nat. Cell Biol. 12 (2010) 909–915.

    Article  PubMed  CAS  Google Scholar 

  68. Sinnett-Smith, J., Lunn, J.A., Leopoldt, D. and Rozengurt, E. Y-27632, an inhibitor of Rho-associated kinases, prevents tyrosine phosphorylation of focal adhesion kinase and paxillin induced by bombesin: dissociation from tyrosine phosphorylation of p130(CAS). Exp. Cell Res. 266 (2001) 292–302.

    Article  PubMed  CAS  Google Scholar 

  69. Ward, M.D. and Hammer, D.A. A theoretical analysis for the effect of focal contact formation on cell-substrate attachment strength. Biophys. J. 64 (1993) 936–959.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  70. Gallant, N.D., Michael, K.E. and Garcia, A.J. Cell adhesion strengthening: contributions of adhesive area, integrin binding, and focal adhesion assembly. Mol. Biol. Cell 16 (2005) 4329–4340.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  71. Stricker, J., Aratyn-Schaus, Y., Oakes, P.W. and Gardel, M.L. Spatiotemporal constraints on the force-dependent growth of focal adhesions. Biophys. J. 100 (2011) 2883–2893.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  72. Coyer, S.R., Singh, A., Dumbauld, D.W., Calderwood, D.A., Craig, S.W., Delamarche, E. and Garcia, A.J. Nanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by integrin activation and cytoskeleton tension. J. Cell Sci. 125 (2012) 5110–5123.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Reinhart-King, C.A., Dembo, M. and Hammer, D.A. The dynamics and mechanics of endothelial cell spreading. Biophys. J. 89 (2005) 676–689.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  74. Schindl, M., Wallraff, E., Deubzer, B., Witke, W., Gerisch, G. and Sackmann, E. Cell-substrate interactions and locomotion of Dictyostelium wild-type and mutants defective in three cytoskeletal proteins: A study using quantitative reflection interference contrast microscopy. Biophys. J. 68 (1995) 1177–1190.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  75. Loomis, W.F., Fuller, D., Gutierrez, E., Groisman, A. and Rappel, W.J. Innate non-specific cell substratum adhesion. PLoS ONE 7 (2012) e42033.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Bereiter-Hahn, J., Strohmeier, R., Kunzenbacher, I., Beck, K. and V”th, M. Locomotion of Xenopus epidermis cells in primary culture. J. Cell Sci. 52 (1981) 289–311.

    PubMed  CAS  Google Scholar 

  77. Lee, J. and Jacobson, K. The composition and dynamics of cell-substratum adhesions in locomoting fish keratocytes. J. Cell Sci. 110 (1997) 2833–2844.

    PubMed  CAS  Google Scholar 

  78. Renkawitz, J., Schumann, K., Weber, M., Lammermann, T., Pflicke, H., Piel, M., Polleux, J., Spatz, J.P. and Sixt, M. Adaptive force transmission in amoeboid cell migration. Nat. Cell Biol. 11 (2009) 1438–1443.

    Article  PubMed  CAS  Google Scholar 

  79. Weiss, L. and Harlos, J.P. Short-term interactions between cell surfaces. Progr. Surf. Sci. 1 (1972) 355–405.

    Article  CAS  Google Scholar 

  80. Curtis, A.S.G. and Büültjens, T.E.J. Cell adhesion and locomotion. Ciba Found. Symp. 4 (1973) 172–186.

    Google Scholar 

  81. Leader, W.M., Stopak, D. and Harris, A.K. Increased contractile strength and tightened adhesions to the substratum result from reverse transformation of CHO cells by dibutyryl cyclic adenosine monophosphate. J. Cell Sci. 64 (1983) 1–11.

    PubMed  CAS  Google Scholar 

  82. Ward, M.D. and Hammer, D.A. Morphology of cell-substratum adhesion. Influence of receptor heterogeneity and nonspecific forces. Cell Biophys. 20 (1992) 177–222.

    Article  PubMed  CAS  Google Scholar 

  83. Abercrombie, M., Heaysman, J.E.M. and Pegrum, S.M. The locomotion of fibroblasts in culture. IV. Electron microscopy of the leading lamella. Exp. Cell Res. 67 (1971) 359–367.

    Article  PubMed  CAS  Google Scholar 

  84. Pegrum, S.M. Contact relationships between chicke embryo cells growing in monolayer culture after infection with Rous sarcoma virus. Exp. Cell Res. 138 (1982) 147–157.

    Article  PubMed  CAS  Google Scholar 

  85. Selhuber-Unkel, C., Erdmann, T., Lopez-Garcia, M., Kessler, H., Schwarz, U.S. and Spatz, J.P. Cell adhesion strength is controlled by intermolecular spacing of adhesion receptors. Biophys. J. 98 (2010) 543–551.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Rees, D.A., Couchman, J.R., Smith, C.G., Woods, A. and Wilson, G. Cellsubstratum interactions in the adhesion and locomotion of fibroblasts. Philos. Trans. R. Soc. Lond. B Biol. Sci. 299 (1982) 169–176.

    Article  PubMed  CAS  Google Scholar 

  87. Woods, A., Smith, C.G., Rees, D.A. and Wilson, G. Stages in specialization of fibroblast adhesion and deposition of extracellular matrix. Eur. J. Cell Biol. 32 (1983) 108–116.

    PubMed  CAS  Google Scholar 

  88. Duband, J.L., Nuckolls, G.H., Ishihara, A., Hasegawa, T., Yamada, K.M., Thiery, J.P. and Jacobson, K. Fibronectin receptor exhibits high lateral mobility in embryonic locomoting cells but is immobile in focal contacts and fibrillar streaks in stationary cells. J. Cell Biol. 107 (1988) 1385–1396.

    Article  PubMed  CAS  Google Scholar 

  89. Bell, G.I., Dembo, M. and Bongrand, P. Cell adhesion: Competition between nonspecific repulsion and specific bonding. Biophys. J. 45 (1984) 1051–1064.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. Abercrombie, M. and Heaysman, J.E.M. Observations on the social behaviour of cells in tissue culture: I. Speed of movement of chick heart fibroblasts in relation to their mutual contacts. Exp. Cell Res. 5 (1953) 111–131.

    Article  PubMed  CAS  Google Scholar 

  91. Abercrombie, M. and Heaysman, J.E.M. Observations on the social behaviour of cells in tissue culture. II. “Monolayering” of fibroblasts. Exp. Cell Res. 6 (1954) 293–306.

    Article  PubMed  CAS  Google Scholar 

  92. Nelson, C.M., Pirone, D.M., Tan, J.L. and Chen, C.S. Vascular endothelialcadherin regulates cytoskeletal tension, cell spreading and focal adhesions by stimulating RhoA. Mol. Biol. Cell 15 (2004) 2943–2953.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Kadir, S., Astin, J.W., Tahtamouni, L., Martin, P. and Nobes, C.D. Microtubule remodelling is required for the front-rear polarity switch during contact inhibition of locomotion. J. Cell Sci. 124 (2011) 2642–2653.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  94. Anear, E. and Parish, R.W. The effects of modifying RhoA and Rac1 activities on heterotypic contact inhibition of locomotion. FEBS Lett. 586 (2012) 1330–1335.

    Article  PubMed  CAS  Google Scholar 

  95. Mayor, R. and Carmona-Fontaine, C. Keeping in touch with contact inhibition of locomotion. Trends Cell Biol. 20 (2010) 319–328.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8

    Arthur Czarnowski, Sylvia Papp, Peter Szaraz & Michal Opas

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King’s College Circle, Medical Sciences Building, room 6326, Toronto, Ontario, M5S 1A8, Canada

    Michal Opas

Authors
  1. Arthur Czarnowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sylvia Papp
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Szaraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michal Opas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michal Opas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czarnowski, A., Papp, S., Szaraz, P. et al. Calreticulin affects cell adhesiveness through differential phosphorylation of insulin receptor substrate-1. Cell Mol Biol Lett 19, 77–97 (2014). https://doi.org/10.2478/s11658-014-0181-9

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11658-014-0181-9

Keywords

Cellular & Molecular Biology Letters

ISSN: 1689-1392

Contact us