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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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.
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.
Bennett, M. K., Erondu, N. E., and Kennedy, M. B. (1983).J. Biol. Chem. 258 12,735–12,744.
Bernhardt, R., and Matus, A. (1982).J. Cell Biol. 92 589–593.
Bernhardt, R., and Matus, A. (1984).J. Comp. Neurol. 226 203–221.
Boyle, W. J., Smeal, T., Defize, L. H. K., Angel, P., Woodgett, J. R., Karin, M., and Hunter, T. (1991).Cell 64 573–584.
Brugg, B., and Matus, A. (1991).J. Cell Biol. 114 735–743.
Burgoyne, R. D., and Cumming, R. (1984).Neurosci. 11 157–167.
Caban, C. E., and Ginsburg, A. (1976).Biochemistry 15 1569–1580.
Caceres, A., Binder, L. I., Payne, M. R., Bender, P., Rebhun, L., and Steward, O. (1984).J. Neurosci. 4 394–410.
Cassimeris, L. V., Wadsworth, P., and Salmon, E. D. (1986).J. Cell Biol. 102 2023–2032.
Chock, P., Rhee, S. G., and Stadtman, E. R. (1980).Annu. Rev. Biochem. 49 813–843.
Cohen, P. (1973).Eur. J. Biochem. 34 1–4.
Dedman, J. R., and Kaetzel, M. A. (1983).Methods Enzymol. 102 1–9.
DeCamilli, P., Miller, P. E., Navone, F., Therkaf, W. E., and Vallee, R. B. (1984).Neurosci. 11 819–846.
DePaoli-Roach, A. A. (1984).J. Biol. Chem. 259 12,144–12,152.
Fischer, E. H., and Krebs, E. G. (1956).J. Biol. Chem. 231 65–71.
Goris, J., Defreyn, G., and Merlevede, W. (1979).FEBS Lett. 99 279–282.
Guan, R. J., Khatra, B. S., and Cohlberg, J. A. (1991).J. Biol. Chem. 266 8262–8267.
Hemmings, B. A., Yellowlees, D., Kernohan, J. C., and Cohen, P. (1981).Eur. J. Biochem. 119 443–451.
Hemmings, B. A., Aitken, A., Cohen, P., Rymond, M., and Hofman, F. (1982).Eur. J. Biochem. 127 473–481.
Hoshi, M., Akiyama, T., Shinohara, Y., Miyata, Y., Ogawara, H., Nishida, E., and Sakai, H. (1988).Eur. J. Biochem. 174 225–230.
Ingebritsen, T. S., and Cohen, P. (1983).Science 221 331–338.
Jameson, L., and Caplow, M. (1981).Proc. Natl. Acad. Sci. USA 78 3413–3417.
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.
Krebs, E. G., Kent, A. B., and Fischer, E. H. (1958).J. Biol. Chem. 233 73–83.
Laemmli, U. K. (1970).Nature 227 680–685.
Laporte, D. C., and Koshland, D. E. (1982).Nature 300 458–460.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951).J. Biol. Chem. 193 265–275.
Mackie, K., Sorkin, B. C., Nairn, A. C., Greengard P., Edelman, G. M., and Cunningham, B. A. (1989).J. Neurosci. 9 1883–1896.
Matus, A. (1988).Annu. Rev. Neurosci. 11 29–44.
Nairn, A. C., Hemmings, H. C., and Greengard, P. (1985).Annu. Rev. Biochem. 54 931–976.
Nishida, E., Kuwaki, T., and Sakai, H. (1981).J. Biochem. 90 575–578.
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.
Reimann, E. M., Walsh, D. A., and Krebs, E. G. (1971).J. Biol. Chem. 246 1986–1995.
Sattilaro, R. F. (1986).Biochemistry 25 2003–2009.
Shelanski, M. L., Gaskin, F., and Cantor, C. R. (1973).Proc. Natl. Acad. Sci. USA 70 765–768.
Stadtman, E. R., and Chock, P. B. (1977).Proc. Natl. Acad. Sci. USA 74 2761–2765.
Stadtman, E. R., and Chock, P. B. (1978).Curr. Top. Cell. Regul. 13 53–95.
Stadtman, E. R., Chock, P. B., and Rhee, S. G. (1981).Curr. Top. Cell. Regul. 18 79–94.
Taniuchi, M., Johnson, E. M. Jr., Roach, P. J., and Lawrence, J. C. Jr. (1986).J. Biol. Chem. 261 13,342–13,349.
Tsuyama, S., Bramblett, G. T., Huang, K.-P., and Flavin, M. (1986).J. Biol. Chem. 261 4110–4116.
Vallee, R. (1980).Proc. Natl. Acad. Sci. USA 77 3206–3210.
Vandenheede, J. R., Yang, S.-D., Goris, J., and Merlevede, W. (1980).J. Biol. Chem. 255 11,768–11,774.
Voter, W. A., O'Brien, T., and Erickson, H. (1991).Cell Motility and the Cytoskeleton 18 55–62.
Weir, J. P., and Frederiksen, D. W. (1982).Methods Enzymol. 85 371–373.
Weingarten, M. D., Lockwood, A. H., Hwo, S., and Krischner, M. W. (1975).Proc. Natl. Acad. Sci. USA 72 1858–1862.
Wiche, G. (1989).Biochem. J. 259 1–12.
Yamamoto, H., Fukunaga, K., Tanaka, E., and Miyamoto, E. (1983).J. Neurochem. 41 1119–1125.
Yamamoto, H., Fukunaga, K., Goto, S., Tanaka, E., and Miyamoto, E. (1985).J. Neurochem. 44 759–768.
Yamamoto, H., Saitoh, Y., Fukunaga, K., Nishimura, H., and Miyamoto, E. (1988).J. Neurochem. 50 1614–1622.
Yang, S.-D., Vandenheede, J. R., Goris, J., and Merlevede, W. (1980).J. Biol. Chim. 255 11,759–11,767.
Yang, S.-D., and Fong, Y.-L. (1985).J. Biol. Chem. 260 13,464–13,470.
Yang, S.-D. (1986).J. Biol. Chem. 261 11,786–11,792.
Yang, S.-D., Liu, J.-S., Fong, Y.-L., Yu, J.-S., and Tzen, T.-C. (1987).J. Neurochem. 48 160–166.
Yang, S.-D., Yu, J.-S., and Lai, Y.-G. (1991a),J. Prot. Chem. 10 171–181.
Yang, S.-D., Benovic, J.-L., Fong, Y.-L., Caron, M. G., and Lefkowitz, R. J. (1991b).Biochem. Biophys. Res. Commun. 178 1306–1311.
Yang, S.-D. (1991).Adv. Prot. Phosphatase 6 133–157.
Yang, S.-D., Song, J.-S., Hsieh, Y.-T., Liu, H.-W., and Chan, W.-H. (1992).J. Prot. Chem. 11 539–546.
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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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DOI: https://doi.org/10.1007/BF01025039