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. 1998 Aug 17;17(16):4887–4902. doi: 10.1093/emboj/17.16.4887

Detergent-salt resistance of LAP2alpha in interphase nuclei and phosphorylation-dependent association with chromosomes early in nuclear assembly implies functions in nuclear structure dynamics.

T Dechat 1, J Gotzmann 1, A Stockinger 1, C A Harris 1, M A Talle 1, J J Siekierka 1, R Foisner 1
PMCID: PMC1170818  PMID: 9707448

Abstract

Lamina-associated polypeptide (LAP) 2 of the inner nuclear membrane (now LAP2beta) and LAP2alpha are related proteins produced by alternative splicing, and contain a common 187 amino acid N-terminal domain. We show here that, unlike LAP2beta, LAP2alpha behaved like a nuclear non-membrane protein in subcellular fractionation studies and was localized throughout the nuclear interior in interphase cells. It co-fractionated with LAP2beta in nuclear lamina/matrix-enriched fractions upon extraction of nuclei with detergent, salt and nucleases. During metaphase LAP2alpha dissociated from chromosomes and became concentrated around the spindle poles. Furthermore, LAP2alpha was mitotically phosphorylated, and phosphorylation correlated with increased LAP2alpha solubility upon extraction of cells in physiological buffers. LAP2alpha relocated to distinct sites around chromosomes at early stages of nuclear reassembly and intermediarily co-localized with peripheral lamin B and intranuclear lamin A structures at telophase. During in vitro nuclear assembly LAP2alpha was dephosphorylated and assembled into insoluble chromatin-associated structures, and recombinant LAP2alpha was found to interact with chromosomes in vitro. Some LAP2alpha may also associate with membranes prior to chromatin attachment. Altogether the data suggest a role of LAP2alpha in post-mitotic nuclear assembly and in the dynamic structural organization of the nucleus.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashery-Padan R., Ulitzur N., Arbel A., Goldberg M., Weiss A. M., Maus N., Fisher P. A., Gruenbaum Y. Localization and posttranslational modifications of otefin, a protein required for vesicle attachment to chromatin, during Drosophila melanogaster development. Mol Cell Biol. 1997 Jul;17(7):4114–4123. doi: 10.1128/mcb.17.7.4114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashery-Padan R., Weiss A. M., Feinstein N., Gruenbaum Y. Distinct regions specify the targeting of otefin to the nucleoplasmic side of the nuclear envelope. J Biol Chem. 1997 Jan 24;272(4):2493–2499. doi: 10.1074/jbc.272.4.2493. [DOI] [PubMed] [Google Scholar]
  3. Bailer S. M., Eppenberger H. M., Griffiths G., Nigg E. A. Characterization of A 54-kD protein of the inner nuclear membrane: evidence for cell cycle-dependent interaction with the nuclear lamina. J Cell Biol. 1991 Aug;114(3):389–400. doi: 10.1083/jcb.114.3.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Belmont A. S., Zhai Y., Thilenius A. Lamin B distribution and association with peripheral chromatin revealed by optical sectioning and electron microscopy tomography. J Cell Biol. 1993 Dec;123(6 Pt 2):1671–1685. doi: 10.1083/jcb.123.6.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berger R., Theodor L., Shoham J., Gokkel E., Brok-Simoni F., Avraham K. B., Copeland N. G., Jenkins N. A., Rechavi G., Simon A. J. The characterization and localization of the mouse thymopoietin/lamina-associated polypeptide 2 gene and its alternatively spliced products. Genome Res. 1996 May;6(5):361–370. doi: 10.1101/gr.6.5.361. [DOI] [PubMed] [Google Scholar]
  6. Bione S., Maestrini E., Rivella S., Mancini M., Regis S., Romeo G., Toniolo D. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet. 1994 Dec;8(4):323–327. doi: 10.1038/ng1294-323. [DOI] [PubMed] [Google Scholar]
  7. Bridger J. M., Kill I. R., O'Farrell M., Hutchison C. J. Internal lamin structures within G1 nuclei of human dermal fibroblasts. J Cell Sci. 1993 Feb;104(Pt 2):297–306. doi: 10.1242/jcs.104.2.297. [DOI] [PubMed] [Google Scholar]
  8. Burke B., Gerace L. A cell free system to study reassembly of the nuclear envelope at the end of mitosis. Cell. 1986 Feb 28;44(4):639–652. doi: 10.1016/0092-8674(86)90273-4. [DOI] [PubMed] [Google Scholar]
  9. Chaudhary N., Courvalin J. C. Stepwise reassembly of the nuclear envelope at the end of mitosis. J Cell Biol. 1993 Jul;122(2):295–306. doi: 10.1083/jcb.122.2.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Compton D. A., Cleveland D. W. NuMA is required for the proper completion of mitosis. J Cell Biol. 1993 Feb;120(4):947–957. doi: 10.1083/jcb.120.4.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Compton D. A., Cleveland D. W. NuMA, a nuclear protein involved in mitosis and nuclear reformation. Curr Opin Cell Biol. 1994 Jun;6(3):343–346. doi: 10.1016/0955-0674(94)90024-8. [DOI] [PubMed] [Google Scholar]
  12. Cordes V. C., Reidenbach S., Rackwitz H. R., Franke W. W. Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments. J Cell Biol. 1997 Feb 10;136(3):515–529. doi: 10.1083/jcb.136.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Courvalin J. C., Segil N., Blobel G., Worman H. J. The lamin B receptor of the inner nuclear membrane undergoes mitosis-specific phosphorylation and is a substrate for p34cdc2-type protein kinase. J Biol Chem. 1992 Sep 25;267(27):19035–19038. [PubMed] [Google Scholar]
  14. Earnshaw W. C., Bernat R. L. Chromosomal passengers: toward an integrated view of mitosis. Chromosoma. 1991 Mar;100(3):139–146. doi: 10.1007/BF00337241. [DOI] [PubMed] [Google Scholar]
  15. Ellenberg J., Siggia E. D., Moreira J. E., Smith C. L., Presley J. F., Worman H. J., Lippincott-Schwartz J. Nuclear membrane dynamics and reassembly in living cells: targeting of an inner nuclear membrane protein in interphase and mitosis. J Cell Biol. 1997 Sep 22;138(6):1193–1206. doi: 10.1083/jcb.138.6.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ellis D. J., Jenkins H., Whitfield W. G., Hutchison C. J. GST-lamin fusion proteins act as dominant negative mutants in Xenopus egg extract and reveal the function of the lamina in DNA replication. J Cell Sci. 1997 Oct;110(Pt 20):2507–2518. doi: 10.1242/jcs.110.20.2507. [DOI] [PubMed] [Google Scholar]
  17. Foisner R. Dynamic organisation of intermediate filaments and associated proteins during the cell cycle. Bioessays. 1997 Apr;19(4):297–305. doi: 10.1002/bies.950190407. [DOI] [PubMed] [Google Scholar]
  18. Foisner R., Gerace L. Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell. 1993 Jul 2;73(7):1267–1279. doi: 10.1016/0092-8674(93)90355-t. [DOI] [PubMed] [Google Scholar]
  19. Foisner R., Traub P., Wiche G. Protein kinase A- and protein kinase C-regulated interaction of plectin with lamin B and vimentin. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3812–3816. doi: 10.1073/pnas.88.9.3812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fricker M., Hollinshead M., White N., Vaux D. Interphase nuclei of many mammalian cell types contain deep, dynamic, tubular membrane-bound invaginations of the nuclear envelope. J Cell Biol. 1997 Feb 10;136(3):531–544. doi: 10.1083/jcb.136.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Furukawa K., Fritze C. E., Gerace L. The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain. J Biol Chem. 1998 Feb 13;273(7):4213–4219. doi: 10.1074/jbc.273.7.4213. [DOI] [PubMed] [Google Scholar]
  22. Furukawa K., Glass C., Kondo T. Characterization of the chromatin binding activity of lamina-associated polypeptide (LAP) 2. Biochem Biophys Res Commun. 1997 Sep 8;238(1):240–246. doi: 10.1006/bbrc.1997.7235. [DOI] [PubMed] [Google Scholar]
  23. Furukawa K., Panté N., Aebi U., Gerace L. Cloning of a cDNA for lamina-associated polypeptide 2 (LAP2) and identification of regions that specify targeting to the nuclear envelope. EMBO J. 1995 Apr 18;14(8):1626–1636. doi: 10.1002/j.1460-2075.1995.tb07151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gaglio T., Saredi A., Compton D. A. NuMA is required for the organization of microtubules into aster-like mitotic arrays. J Cell Biol. 1995 Nov;131(3):693–708. doi: 10.1083/jcb.131.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gant T. M., Wilson K. L. Nuclear assembly. Annu Rev Cell Dev Biol. 1997;13:669–695. doi: 10.1146/annurev.cellbio.13.1.669. [DOI] [PubMed] [Google Scholar]
  26. Georgatos S. D., Meier J., Simos G. Lamins and lamin-associated proteins. Curr Opin Cell Biol. 1994 Jun;6(3):347–353. doi: 10.1016/0955-0674(94)90025-6. [DOI] [PubMed] [Google Scholar]
  27. Gerace L., Burke B. Functional organization of the nuclear envelope. Annu Rev Cell Biol. 1988;4:335–374. doi: 10.1146/annurev.cb.04.110188.002003. [DOI] [PubMed] [Google Scholar]
  28. Gerace L., Foisner R. Integral membrane proteins and dynamic organization of the nuclear envelope. Trends Cell Biol. 1994 Apr;4(4):127–131. doi: 10.1016/0962-8924(94)90067-1. [DOI] [PubMed] [Google Scholar]
  29. Glass C. A., Glass J. R., Taniura H., Hasel K. W., Blevitt J. M., Gerace L. The alpha-helical rod domain of human lamins A and C contains a chromatin binding site. EMBO J. 1993 Nov;12(11):4413–4424. doi: 10.1002/j.1460-2075.1993.tb06126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Glass J. R., Gerace L. Lamins A and C bind and assemble at the surface of mitotic chromosomes. J Cell Biol. 1990 Sep;111(3):1047–1057. doi: 10.1083/jcb.111.3.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Goldberg M. W., Allen T. D. High resolution scanning electron microscopy of the nuclear envelope: demonstration of a new, regular, fibrous lattice attached to the baskets of the nucleoplasmic face of the nuclear pores. J Cell Biol. 1992 Dec;119(6):1429–1440. doi: 10.1083/jcb.119.6.1429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Goldberg M., Jenkins H., Allen T., Whitfield W. G., Hutchison C. J. Xenopus lamin B3 has a direct role in the assembly of a replication competent nucleus: evidence from cell-free egg extracts. J Cell Sci. 1995 Nov;108(Pt 11):3451–3461. doi: 10.1242/jcs.108.11.3451. [DOI] [PubMed] [Google Scholar]
  33. Gotzmann J., Eger A., Meissner M., Grimm R., Gerner C., Sauermann G., Foisner R. Two-dimensional electrophoresis reveals a nuclear matrix-associated nucleolin complex of basic isoelectric point. Electrophoresis. 1997 Dec;18(14):2645–2653. doi: 10.1002/elps.1150181421. [DOI] [PubMed] [Google Scholar]
  34. Harris C. A., Andryuk P. J., Cline S. W., Mathew S., Siekierka J. J., Goldstein G. Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2. Genomics. 1995 Jul 20;28(2):198–205. doi: 10.1006/geno.1995.1131. [DOI] [PubMed] [Google Scholar]
  35. Harris C. A., Andryuk P. J., Cline S., Chan H. K., Natarajan A., Siekierka J. J., Goldstein G. Three distinct human thymopoietins are derived from alternatively spliced mRNAs. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6283–6287. doi: 10.1073/pnas.91.14.6283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Hozák P., Sasseville A. M., Raymond Y., Cook P. R. Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. J Cell Sci. 1995 Feb;108(Pt 2):635–644. doi: 10.1242/jcs.108.2.635. [DOI] [PubMed] [Google Scholar]
  37. Höger T. H., Krohne G., Kleinschmidt J. A. Interaction of Xenopus lamins A and LII with chromatin in vitro mediated by a sequence element in the carboxyterminal domain. Exp Cell Res. 1991 Dec;197(2):280–289. doi: 10.1016/0014-4827(91)90434-v. [DOI] [PubMed] [Google Scholar]
  38. Kallajoki M., Harborth J., Weber K., Osborn M. Microinjection of a monoclonal antibody against SPN antigen, now identified by peptide sequences as the NuMA protein, induces micronuclei in PtK2 cells. J Cell Sci. 1993 Jan;104(Pt 1):139–150. doi: 10.1242/jcs.104.1.139. [DOI] [PubMed] [Google Scholar]
  39. Krauss S. W., Larabell C. A., Lockett S., Gascard P., Penman S., Mohandas N., Chasis J. A. Structural protein 4.1 in the nucleus of human cells: dynamic rearrangements during cell division. J Cell Biol. 1997 Apr 21;137(2):275–289. doi: 10.1083/jcb.137.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  41. Lourim D., Krohne G. Lamin-dependent nuclear envelope reassembly following mitosis: an argument. Trends Cell Biol. 1994 Sep;4(9):314–318. doi: 10.1016/0962-8924(94)90228-3. [DOI] [PubMed] [Google Scholar]
  42. Maison C., Pyrpasopoulou A., Georgatos S. D. Vimentin-associated mitotic vesicles interact with chromosomes in a lamin B- and phosphorylation-dependent manner. EMBO J. 1995 Jul 17;14(14):3311–3324. doi: 10.1002/j.1460-2075.1995.tb07338.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Maison C., Pyrpasopoulou A., Theodoropoulos P. A., Georgatos S. D. The inner nuclear membrane protein LAP1 forms a native complex with B-type lamins and partitions with spindle-associated mitotic vesicles. EMBO J. 1997 Aug 15;16(16):4839–4850. doi: 10.1093/emboj/16.16.4839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Manilal S., Nguyen T. M., Sewry C. A., Morris G. E. The Emery-Dreifuss muscular dystrophy protein, emerin, is a nuclear membrane protein. Hum Mol Genet. 1996 Jun;5(6):801–808. doi: 10.1093/hmg/5.6.801. [DOI] [PubMed] [Google Scholar]
  45. Marshall I. C., Wilson K. L. Nuclear envelope assembly after mitosis. Trends Cell Biol. 1997 Feb;7(2):69–74. doi: 10.1016/S0962-8924(96)10047-7. [DOI] [PubMed] [Google Scholar]
  46. Martin L., Crimaudo C., Gerace L. cDNA cloning and characterization of lamina-associated polypeptide 1C (LAP1C), an integral protein of the inner nuclear membrane. J Biol Chem. 1995 Apr 14;270(15):8822–8828. doi: 10.1074/jbc.270.15.8822. [DOI] [PubMed] [Google Scholar]
  47. Meier J., Georgatos S. D. Type B lamins remain associated with the integral nuclear envelope protein p58 during mitosis: implications for nuclear reassembly. EMBO J. 1994 Apr 15;13(8):1888–1898. doi: 10.1002/j.1460-2075.1994.tb06458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Merdes A., Ramyar K., Vechio J. D., Cleveland D. W. A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. Cell. 1996 Nov 1;87(3):447–458. doi: 10.1016/s0092-8674(00)81365-3. [DOI] [PubMed] [Google Scholar]
  49. Moir R. D., Montag-Lowy M., Goldman R. D. Dynamic properties of nuclear lamins: lamin B is associated with sites of DNA replication. J Cell Biol. 1994 Jun;125(6):1201–1212. doi: 10.1083/jcb.125.6.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Moir R. D., Spann T. P., Goldman R. D. The dynamic properties and possible functions of nuclear lamins. Int Rev Cytol. 1995;162B:141–182. doi: 10.1016/s0074-7696(08)62616-9. [DOI] [PubMed] [Google Scholar]
  51. Nagano A., Koga R., Ogawa M., Kurano Y., Kawada J., Okada R., Hayashi Y. K., Tsukahara T., Arahata K. Emerin deficiency at the nuclear membrane in patients with Emery-Dreifuss muscular dystrophy. Nat Genet. 1996 Mar;12(3):254–259. doi: 10.1038/ng0396-254. [DOI] [PubMed] [Google Scholar]
  52. Newport J. W., Wilson K. L., Dunphy W. G. A lamin-independent pathway for nuclear envelope assembly. J Cell Biol. 1990 Dec;111(6 Pt 1):2247–2259. doi: 10.1083/jcb.111.6.2247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Nickerson J. A., Krockmalnic G., Wan K. M., Penman S. The nuclear matrix revealed by eluting chromatin from a cross-linked nucleus. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4446–4450. doi: 10.1073/pnas.94.9.4446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Nickerson J. A., Krockmalnic G., Wan K. M., Turner C. D., Penman S. A normally masked nuclear matrix antigen that appears at mitosis on cytoskeleton filaments adjoining chromosomes, centrioles, and midbodies. J Cell Biol. 1992 Feb;116(4):977–987. doi: 10.1083/jcb.116.4.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Nigg E. A. Assembly-disassembly of the nuclear lamina. Curr Opin Cell Biol. 1992 Feb;4(1):105–109. doi: 10.1016/0955-0674(92)90066-l. [DOI] [PubMed] [Google Scholar]
  56. Nikolakaki E., Meier J., Simos G., Georgatos S. D., Giannakouros T. Mitotic phosphorylation of the lamin B receptor by a serine/arginine kinase and p34(cdc2). J Biol Chem. 1997 Mar 7;272(10):6208–6213. doi: 10.1074/jbc.272.10.6208. [DOI] [PubMed] [Google Scholar]
  57. Ottaviano Y., Gerace L. Phosphorylation of the nuclear lamins during interphase and mitosis. J Biol Chem. 1985 Jan 10;260(1):624–632. [PubMed] [Google Scholar]
  58. Padan R., Nainudel-Epszteyn S., Goitein R., Fainsod A., Gruenbaum Y. Isolation and characterization of the Drosophila nuclear envelope otefin cDNA. J Biol Chem. 1990 May 15;265(14):7808–7813. [PubMed] [Google Scholar]
  59. Paddy M. R., Belmont A. S., Saumweber H., Agard D. A., Sedat J. W. Interphase nuclear envelope lamins form a discontinuous network that interacts with only a fraction of the chromatin in the nuclear periphery. Cell. 1990 Jul 13;62(1):89–106. doi: 10.1016/0092-8674(90)90243-8. [DOI] [PubMed] [Google Scholar]
  60. Pyrpasopoulou A., Meier J., Maison C., Simos G., Georgatos S. D. The lamin B receptor (LBR) provides essential chromatin docking sites at the nuclear envelope. EMBO J. 1996 Dec 16;15(24):7108–7119. [PMC free article] [PubMed] [Google Scholar]
  61. Senior A., Gerace L. Integral membrane proteins specific to the inner nuclear membrane and associated with the nuclear lamina. J Cell Biol. 1988 Dec;107(6 Pt 1):2029–2036. doi: 10.1083/jcb.107.6.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Spann T. P., Moir R. D., Goldman A. E., Stick R., Goldman R. D. Disruption of nuclear lamin organization alters the distribution of replication factors and inhibits DNA synthesis. J Cell Biol. 1997 Mar 24;136(6):1201–1212. doi: 10.1083/jcb.136.6.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Taniura H., Glass C., Gerace L. A chromatin binding site in the tail domain of nuclear lamins that interacts with core histones. J Cell Biol. 1995 Oct;131(1):33–44. doi: 10.1083/jcb.131.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Worman H. J., Evans C. D., Blobel G. The lamin B receptor of the nuclear envelope inner membrane: a polytopic protein with eight potential transmembrane domains. J Cell Biol. 1990 Oct;111(4):1535–1542. doi: 10.1083/jcb.111.4.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Worman H. J., Yuan J., Blobel G., Georgatos S. D. A lamin B receptor in the nuclear envelope. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8531–8534. doi: 10.1073/pnas.85.22.8531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Yang L., Guan T., Gerace L. Integral membrane proteins of the nuclear envelope are dispersed throughout the endoplasmic reticulum during mitosis. J Cell Biol. 1997 Jun 16;137(6):1199–1210. doi: 10.1083/jcb.137.6.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Yang L., Guan T., Gerace L. Lamin-binding fragment of LAP2 inhibits increase in nuclear volume during the cell cycle and progression into S phase. J Cell Biol. 1997 Dec 1;139(5):1077–1087. doi: 10.1083/jcb.139.5.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Ye Q., Callebaut I., Pezhman A., Courvalin J. C., Worman H. J. Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR. J Biol Chem. 1997 Jun 6;272(23):14983–14989. doi: 10.1074/jbc.272.23.14983. [DOI] [PubMed] [Google Scholar]
  69. Ye Q., Worman H. J. Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1. J Biol Chem. 1996 Jun 21;271(25):14653–14656. doi: 10.1074/jbc.271.25.14653. [DOI] [PubMed] [Google Scholar]
  70. Yuan J., Simos G., Blobel G., Georgatos S. D. Binding of lamin A to polynucleosomes. J Biol Chem. 1991 May 15;266(14):9211–9215. [PubMed] [Google Scholar]

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