Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 2001 Jul 15;357(Pt 2):569–574. doi: 10.1042/0264-6021:3570569

Extracellular processing of amphoterin generates a peptide active on erythroleukaemia cell differentiation.

B Sparatore 1, M Patrone 1, M Passalacqua 1, M Pedrazzi 1, D Gaggero 1, S Pontremoli 1, E Melloni 1
PMCID: PMC1221987  PMID: 11439110

Abstract

The release of amphoterin by murine erythroleukaemia cells exposed to the chemical inducer hexamethylenebisacetamide represents an essential step for the process of their terminal differentiation. Once exported in the culture medium, amphoterin undergoes limited proteolysis, catalysed by a serine proteinase also secreted by stimulated cells. The isolated proteinase is responsible for degradation of amphoterin, with the production of a 10-amino-acid-residue fragment, specifically retaining the cell-differentiation-stimulating activity of the native protein molecule. This peptide does not express other properties of amphoterin, such as protein kinase C-stimulating activity or systemic toxicity. These findings define a selective mechanism accounting for extracellular amphoterin functional maturation.

Full Text

The Full Text of this article is available as a PDF (138.7 KB).

Selected References

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

  1. Abraham E., Arcaroli J., Carmody A., Wang H., Tracey K. J. HMG-1 as a mediator of acute lung inflammation. J Immunol. 2000 Sep 15;165(6):2950–2954. doi: 10.4049/jimmunol.165.6.2950. [DOI] [PubMed] [Google Scholar]
  2. Andersson U., Wang H., Palmblad K., Aveberger A. C., Bloom O., Erlandsson-Harris H., Janson A., Kokkola R., Zhang M., Yang H. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000 Aug 21;192(4):565–570. doi: 10.1084/jem.192.4.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bianchi M. E., Beltrame M., Paonessa G. Specific recognition of cruciform DNA by nuclear protein HMG1. Science. 1989 Feb 24;243(4894 Pt 1):1056–1059. doi: 10.1126/science.2922595. [DOI] [PubMed] [Google Scholar]
  4. Bieth J., Spiess B., Wermuth C. G. The synthesis and analytical use of a highly sensitive and convenient substrate of elastase. Biochem Med. 1974 Dec;11(4):350–357. doi: 10.1016/0006-2944(74)90134-3. [DOI] [PubMed] [Google Scholar]
  5. Collen D., Lijnen H. R., De Cock F., Durieux J. P., Loffet A. Kinetic properties of tripeptide lysyl chloromethyl ketone and lysyl p-nitroanilide derivatives towards trypsin-like serine proteinases. Biochim Biophys Acta. 1980 Sep 9;615(1):158–166. doi: 10.1016/0005-2744(80)90019-4. [DOI] [PubMed] [Google Scholar]
  6. Ellwood K. B., Yen Y. M., Johnson R. C., Carey M. Mechanism for specificity by HMG-1 in enhanceosome assembly. Mol Cell Biol. 2000 Jun;20(12):4359–4370. doi: 10.1128/mcb.20.12.4359-4370.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fages C., Nolo R., Huttunen H. J., Eskelinen E., Rauvala H. Regulation of cell migration by amphoterin. J Cell Sci. 2000 Feb;113(Pt 4):611–620. doi: 10.1242/jcs.113.4.611. [DOI] [PubMed] [Google Scholar]
  8. Gaertner H. F., Puigserver A. J. Increased activity and stability of poly(ethylene glycol)-modified trypsin. Enzyme Microb Technol. 1992 Feb;14(2):150–155. doi: 10.1016/0141-0229(92)90174-m. [DOI] [PubMed] [Google Scholar]
  9. Hori O., Brett J., Slattery T., Cao R., Zhang J., Chen J. X., Nagashima M., Lundh E. R., Vijay S., Nitecki D. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem. 1995 Oct 27;270(43):25752–25761. doi: 10.1074/jbc.270.43.25752. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Landsman D., Bustin M. Assessment of the transcriptional activation potential of the HMG chromosomal proteins. Mol Cell Biol. 1991 Sep;11(9):4483–4489. doi: 10.1128/mcb.11.9.4483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Melloni E., Pontremoli S., Michetti M., Sacco O., Cakiroglu A. G., Jackson J. F., Rifkind R. A., Marks P. A. Protein kinase C activity and hexamethylenebisacetamide-induced erythroleukemia cell differentiation. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5282–5286. doi: 10.1073/pnas.84.15.5282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Melloni E., Pontremoli S., Viotti P. L., Patrone M., Marks P. A., Rifkind R. A. Differential expression of protein kinase C isozymes and erythroleukemia cell differentiation. J Biol Chem. 1989 Nov 5;264(31):18414–18418. [PubMed] [Google Scholar]
  14. Melloni E., Sparatore B., Patrone M., Pessino A., Passalacqua M., Pontremoli S. Extracellular release of the 'differentiation enhancing factor', a HMG1 protein type, is an early step in murine erythroleukemia cell differentiation. FEBS Lett. 1995 Jul 24;368(3):466–470. doi: 10.1016/0014-5793(95)00716-m. [DOI] [PubMed] [Google Scholar]
  15. Merenmies J., Pihlaskari R., Laitinen J., Wartiovaara J., Rauvala H. 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. J Biol Chem. 1991 Sep 5;266(25):16722–16729. [PubMed] [Google Scholar]
  16. Michetti M., Salamino F., Tedesco I., Averna M., Minafra R., Melloni E., Pontremoli S. Autolysis of human erythrocyte calpain produces two active enzyme forms with different cell localization. FEBS Lett. 1996 Aug 19;392(1):11–15. doi: 10.1016/0014-5793(96)00775-2. [DOI] [PubMed] [Google Scholar]
  17. Nakajima K., Powers J. C., Ashe B. M., Zimmerman M. Mapping the extended substrate binding site of cathepsin G and human leukocyte elastase. Studies with peptide substrates related to the alpha 1-protease inhibitor reactive site. J Biol Chem. 1979 May 25;254(10):4027–4032. [PubMed] [Google Scholar]
  18. Parkkinen J., Raulo E., Merenmies J., Nolo R., Kajander E. O., Baumann M., Rauvala H. Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. J Biol Chem. 1993 Sep 15;268(26):19726–19738. [PubMed] [Google Scholar]
  19. Parkkinen J., Rauvala H. Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin. J Biol Chem. 1991 Sep 5;266(25):16730–16735. [PubMed] [Google Scholar]
  20. Passalacqua M., Patrone M., Picotti G. B., Del Rio M., Sparatore B., Melloni E., Pontremoli S. Stimulated astrocytes release high-mobility group 1 protein, an inducer of LAN-5 neuroblastoma cell differentiation. Neuroscience. 1998 Feb;82(4):1021–1028. doi: 10.1016/s0306-4522(97)00352-7. [DOI] [PubMed] [Google Scholar]
  21. Passalacqua M., Zicca A., Sparatore B., Patrone M., Melloni E., Pontremoli S. Secretion and binding of HMG1 protein to the external surface of the membrane are required for murine erythroleukemia cell differentiation. FEBS Lett. 1997 Jan 6;400(3):275–279. doi: 10.1016/s0014-5793(96)01402-0. [DOI] [PubMed] [Google Scholar]
  22. Rauvala H., Pihlaskari R. Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons. J Biol Chem. 1987 Dec 5;262(34):16625–16635. [PubMed] [Google Scholar]
  23. Sparatore B., Passalacqua M., Patrone M., Melloni E., Pontremoli S. Extracellular high-mobility group 1 protein is essential for murine erythroleukaemia cell differentiation. Biochem J. 1996 Nov 15;320(Pt 1):253–256. doi: 10.1042/bj3200253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Taguchi A., Blood D. C., del Toro G., Canet A., Lee D. C., Qu W., Tanji N., Lu Y., Lalla E., Fu C. Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature. 2000 May 18;405(6784):354–360. doi: 10.1038/35012626. [DOI] [PubMed] [Google Scholar]
  25. WINTERHALTER K. H., HUEHNS E. R. PREPARATIONS, PROPERTIES, AND SPECIFIC RECOMBINATION OF ALPHA-BETA-GLOBIN SUBUNITS. J Biol Chem. 1964 Nov;239:3699–3705. [PubMed] [Google Scholar]
  26. Wang H., Bloom O., Zhang M., Vishnubhakat J. M., Ombrellino M., Che J., Frazier A., Yang H., Ivanova S., Borovikova L. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999 Jul 9;285(5425):248–251. doi: 10.1126/science.285.5425.248. [DOI] [PubMed] [Google Scholar]
  27. Wang H., Vishnubhakat J. M., Bloom O., Zhang M., Ombrellino M., Sama A., Tracey K. J. Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes. Surgery. 1999 Aug;126(2):389–392. [PubMed] [Google Scholar]
  28. Weir H. M., Kraulis P. J., Hill C. S., Raine A. R., Laue E. D., Thomas J. O. Structure of the HMG box motif in the B-domain of HMG1. EMBO J. 1993 Apr;12(4):1311–1319. doi: 10.1002/j.1460-2075.1993.tb05776.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES