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Cyclic modulation of cross-linking interactions of microtubule-associated protein-2 with actin and microtubules by protein kinase FA

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Abstract

The ATP.Mg-dependent type-1 protein phosphatase activating factor (factor FA) was identified as a brain protein kinase that could phosphorylate microtubule-associated protein-2 (MAP-2) and thereby inhibit cross-linking interactions of MAP-2 with actin filaments and microtubules isolated from porcine brain. The phosphorylation sites were found to be equally located on both projection and microtubule-binding domains of MAP-2. Phosphoamino acid analysis revealed that the phosphorylation sites were on both serine and threonine residues, indicating that factor FA is a serine/threonine-specific MAP-2 kinase. Conversely, factor FA was further identified as a MAP-2 phosphatase activator that could promote the dephosphorylation of32P-MAP-2 phosphorylated by factor FA itself and thereby potentiate cross-linking interactions of MAP-2 with actin and microtubules. Furthermore, the two opposing functions of factor FA can be selectively modulated in a reciprocal manner bypH change. For instance, alkalinepH could stimulate factor FA to work as a MAP-2 kinase but simultaneously block it to work as a MAP-2 phosphatase activator to potentiate the inhibition on the cross-linking interactions of MAP-2 with actin and microtubules. Taken together, the results provide initial evidence that a cyclic modulation of cross-linking interactions of MAP-2 with actin filaments and microtubules can be controlled by factor FA, representing an efficient cyclic cascade control mechanism for rapid structural and functional regulation of neuronal cytoskeletal system.

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References

  • Akiyama, T., Nishida, E., Ishida, J., Saji, N., Ogawara, H., Hoshi, M., Miyata, Y. and Sakai, H. (1986a).J. Biol. Chem. 261 15,648–15,651.

    CAS  Google Scholar 

  • Akiyama, T., Kadowaki, T., Nishida, E., Kadooka, T., Ogawara, H., Fukami, Y., Sakai, H., Takaku, F. and Kasuga, M. (1986b).J. Biol. Chem. 261 14,797–14,803.

    CAS  Google Scholar 

  • Bennett, M. K., Erondu, N. E., and Kennedy, M. B. (1983).J. Biol. Chem. 258 12,735–12,744.

    CAS  Google Scholar 

  • Bernhardt, R., and Matus, A. (1982).J. Cell Biol. 92 589–593.

    CAS  PubMed  Google Scholar 

  • Bernhardt, R., and Matus, A. (1984).J. Comp. Neurol. 226 203–221.

    CAS  PubMed  Google Scholar 

  • Boyle, W. J., Smeal, T., Defize, L. H. K., Angel, P., Woodgett, J. R., Karin, M., and Hunter, T. (1991).Cell 64 573–584.

    CAS  PubMed  Google Scholar 

  • Brugg, B., and Matus, A. (1991).J. Cell Biol. 114 735–743.

    CAS  PubMed  Google Scholar 

  • Burgoyne, R. D., and Cumming, R. (1984).Neurosci. 11 157–167.

    CAS  Google Scholar 

  • Caban, C. E., and Ginsburg, A. (1976).Biochemistry 15 1569–1580.

    CAS  PubMed  Google Scholar 

  • Caceres, A., Binder, L. I., Payne, M. R., Bender, P., Rebhun, L., and Steward, O. (1984).J. Neurosci. 4 394–410.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cassimeris, L. V., Wadsworth, P., and Salmon, E. D. (1986).J. Cell Biol. 102 2023–2032.

    CAS  PubMed  Google Scholar 

  • Chock, P., Rhee, S. G., and Stadtman, E. R. (1980).Annu. Rev. Biochem. 49 813–843.

    CAS  PubMed  Google Scholar 

  • Cohen, P. (1973).Eur. J. Biochem. 34 1–4.

    CAS  PubMed  Google Scholar 

  • Dedman, J. R., and Kaetzel, M. A. (1983).Methods Enzymol. 102 1–9.

    CAS  PubMed  Google Scholar 

  • DeCamilli, P., Miller, P. E., Navone, F., Therkaf, W. E., and Vallee, R. B. (1984).Neurosci. 11 819–846.

    Google Scholar 

  • DePaoli-Roach, A. A. (1984).J. Biol. Chem. 259 12,144–12,152.

    Google Scholar 

  • Fischer, E. H., and Krebs, E. G. (1956).J. Biol. Chem. 231 65–71.

    Google Scholar 

  • Goris, J., Defreyn, G., and Merlevede, W. (1979).FEBS Lett. 99 279–282.

    CAS  PubMed  Google Scholar 

  • Guan, R. J., Khatra, B. S., and Cohlberg, J. A. (1991).J. Biol. Chem. 266 8262–8267.

    CAS  PubMed  Google Scholar 

  • Hemmings, B. A., Yellowlees, D., Kernohan, J. C., and Cohen, P. (1981).Eur. J. Biochem. 119 443–451.

    CAS  PubMed  Google Scholar 

  • Hemmings, B. A., Aitken, A., Cohen, P., Rymond, M., and Hofman, F. (1982).Eur. J. Biochem. 127 473–481.

    CAS  PubMed  Google Scholar 

  • Hoshi, M., Akiyama, T., Shinohara, Y., Miyata, Y., Ogawara, H., Nishida, E., and Sakai, H. (1988).Eur. J. Biochem. 174 225–230.

    CAS  PubMed  Google Scholar 

  • Ingebritsen, T. S., and Cohen, P. (1983).Science 221 331–338.

    CAS  PubMed  Google Scholar 

  • Jameson, L., and Caplow, M. (1981).Proc. Natl. Acad. Sci. USA 78 3413–3417.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kadowaki, T., Fujita-Yamaguchi, Y., Nishida, E., Takaku, F., Akiyama, T., Kathuria, S., Akanuma, Y., and Kasuga, M. (1985).J. Bioi. Chem. 260 4016–4020.

    CAS  Google Scholar 

  • Krebs, E. G., Kent, A. B., and Fischer, E. H. (1958).J. Biol. Chem. 233 73–83.

    Google Scholar 

  • Laemmli, U. K. (1970).Nature 227 680–685.

    CAS  PubMed  Google Scholar 

  • Laporte, D. C., and Koshland, D. E. (1982).Nature 300 458–460.

    CAS  PubMed  Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951).J. Biol. Chem. 193 265–275.

    CAS  PubMed  Google Scholar 

  • Mackie, K., Sorkin, B. C., Nairn, A. C., Greengard P., Edelman, G. M., and Cunningham, B. A. (1989).J. Neurosci. 9 1883–1896.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matus, A. (1988).Annu. Rev. Neurosci. 11 29–44.

    CAS  PubMed  Google Scholar 

  • Nairn, A. C., Hemmings, H. C., and Greengard, P. (1985).Annu. Rev. Biochem. 54 931–976.

    CAS  PubMed  Google Scholar 

  • Nishida, E., Kuwaki, T., and Sakai, H. (1981).J. Biochem. 90 575–578.

    CAS  PubMed  Google Scholar 

  • Nishida, E., Hoshi, M., Miyata, Y., Sakai, H., Kadowaki, T., Kasuga, M., Saijo, S., Ogawara, H., and Akiyama, T. (1987).J. Biol. Chem. 262 16,200–16,204.

    CAS  Google Scholar 

  • Reimann, E. M., Walsh, D. A., and Krebs, E. G. (1971).J. Biol. Chem. 246 1986–1995.

    CAS  PubMed  Google Scholar 

  • Sattilaro, R. F. (1986).Biochemistry 25 2003–2009.

    CAS  PubMed  Google Scholar 

  • Shelanski, M. L., Gaskin, F., and Cantor, C. R. (1973).Proc. Natl. Acad. Sci. USA 70 765–768.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stadtman, E. R., and Chock, P. B. (1977).Proc. Natl. Acad. Sci. USA 74 2761–2765.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stadtman, E. R., and Chock, P. B. (1978).Curr. Top. Cell. Regul. 13 53–95.

    CAS  PubMed  Google Scholar 

  • Stadtman, E. R., Chock, P. B., and Rhee, S. G. (1981).Curr. Top. Cell. Regul. 18 79–94.

    CAS  PubMed  Google Scholar 

  • Taniuchi, M., Johnson, E. M. Jr., Roach, P. J., and Lawrence, J. C. Jr. (1986).J. Biol. Chem. 261 13,342–13,349.

    CAS  Google Scholar 

  • Tsuyama, S., Bramblett, G. T., Huang, K.-P., and Flavin, M. (1986).J. Biol. Chem. 261 4110–4116.

    CAS  PubMed  Google Scholar 

  • Vallee, R. (1980).Proc. Natl. Acad. Sci. USA 77 3206–3210.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vandenheede, J. R., Yang, S.-D., Goris, J., and Merlevede, W. (1980).J. Biol. Chem. 255 11,768–11,774.

    CAS  Google Scholar 

  • Voter, W. A., O'Brien, T., and Erickson, H. (1991).Cell Motility and the Cytoskeleton 18 55–62.

    CAS  PubMed  Google Scholar 

  • Weir, J. P., and Frederiksen, D. W. (1982).Methods Enzymol. 85 371–373.

    CAS  PubMed  Google Scholar 

  • Weingarten, M. D., Lockwood, A. H., Hwo, S., and Krischner, M. W. (1975).Proc. Natl. Acad. Sci. USA 72 1858–1862.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wiche, G. (1989).Biochem. J. 259 1–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamoto, H., Fukunaga, K., Tanaka, E., and Miyamoto, E. (1983).J. Neurochem. 41 1119–1125.

    CAS  PubMed  Google Scholar 

  • Yamamoto, H., Fukunaga, K., Goto, S., Tanaka, E., and Miyamoto, E. (1985).J. Neurochem. 44 759–768.

    CAS  PubMed  Google Scholar 

  • Yamamoto, H., Saitoh, Y., Fukunaga, K., Nishimura, H., and Miyamoto, E. (1988).J. Neurochem. 50 1614–1622.

    CAS  PubMed  Google Scholar 

  • Yang, S.-D., Vandenheede, J. R., Goris, J., and Merlevede, W. (1980).J. Biol. Chim. 255 11,759–11,767.

    CAS  Google Scholar 

  • Yang, S.-D., and Fong, Y.-L. (1985).J. Biol. Chem. 260 13,464–13,470.

    CAS  Google Scholar 

  • Yang, S.-D. (1986).J. Biol. Chem. 261 11,786–11,792.

    CAS  Google Scholar 

  • Yang, S.-D., Liu, J.-S., Fong, Y.-L., Yu, J.-S., and Tzen, T.-C. (1987).J. Neurochem. 48 160–166.

    CAS  PubMed  Google Scholar 

  • Yang, S.-D., Yu, J.-S., and Lai, Y.-G. (1991a),J. Prot. Chem. 10 171–181.

    CAS  Google Scholar 

  • Yang, S.-D., Benovic, J.-L., Fong, Y.-L., Caron, M. G., and Lefkowitz, R. J. (1991b).Biochem. Biophys. Res. Commun. 178 1306–1311.

    CAS  PubMed  Google Scholar 

  • Yang, S.-D. (1991).Adv. Prot. Phosphatase 6 133–157.

    CAS  Google Scholar 

  • Yang, S.-D., Song, J.-S., Hsieh, Y.-T., Liu, H.-W., and Chan, W.-H. (1992).J. Prot. Chem. 11 539–546.

    CAS  Google Scholar 

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Yang, SD., Song, JS., Liu, HW. et al. Cyclic modulation of cross-linking interactions of microtubule-associated protein-2 with actin and microtubules by protein kinase FA. J Protein Chem 12, 393–402 (1993). https://doi.org/10.1007/BF01025039

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