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Gene Review

A2m  -  alpha-2-macroglobulin

Mus musculus

Synonyms: A2mp, Alpha-2-macroglobulin, Alpha-2-macroglobulin-P
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Disease relevance of A2m


High impact information on A2m

  • Rapid acidification of endocytic vesicles containing alpha 2-macroglobulin [6].
  • Using alpha 2-macroglobulin as the ligand and electron microscopic cytochemical methods, we have shown the unusual appearance of this previously undescribed organelle and have followed the labeled ligand in these vesicles in the cytoplasm [7].
  • The internalization of a wide range of biologically significant macromolecules, particularly low density lipoproteins (LDL) and proteins such as alpha 2-macroglobulin and epidermal growth factor, occurs primarily through characteristic, bristle-coated indentations of the cell surface known as coated pits [8].
  • Receptors for maleylated or acetylated proteins as well as for alpha-2-macroglobulin-protease complexes on macrophages serve as scavengers by mediating the uptake of macromolecules from the extracellular compartment [9].
  • The resulting alpha 2M preparations still bound 125I-TGF-beta 1; however, the complexes did not clear when injected intravenously in mice [10].

Chemical compound and disease context of A2m

  • An increase in the plasma concentrations of complement factors C1, C3c, C4 and C5, factor B and alpha-2-macroglobulin suggested that an acute phase response and activation of the complement system had occurred as a result of the infection [11].

Biological context of A2m


Anatomical context of A2m


Associations of A2m with chemical compounds

  • No inhibition was observed for the binding of 125I-labeled methylamine-activated alpha 2-macroglobulin or [125I]t-PA.PAI-1 to LRP [21].
  • Binding of alpha 2M-methylamine to low density lipoprotein-related protein (LRP) results in cellular uptake and degradation, while binding to a newly described alpha 2M signaling receptor elevates intracellular calcium ([Ca2+]i) and inositol phosphates [18].
  • Nondenaturing polyacrylamide gel electrophoresis showed that plasmin converted alpha 2M to its electrophoretically "fast" form at a 2:1 molar ratio and that 125I-PDGF-BB bound both alpha 2M and alpha 2M-plasmin [22].
  • As observed for total [3H]eicosanoid secretion, alpha 2M 'fast' forms also rapidly enhanced the secretion of the cAMP-elevating prostanoid, prostaglandin E2, from resident peritoneal macrophages [23].
  • 0. Intensities of cells were measured using a microscope spectrofluorometer after internalization of fluorescein-labeled alpha 2-macroglobulin by receptor-mediated endocytosis [24].

Physical interactions of A2m

  • Radiolabeled lysozyme was internalized more rapidly and to a greater extent when bound to alpha 2M than when unbound [25].

Regulatory relationships of A2m


Other interactions of A2m


Analytical, diagnostic and therapeutic context of A2m


  1. Clonal variation in the production of tumor-associated alpha 2-macroglobulin in a malignant human melanoma and association with growth stimulation. Bízik, J., Lizonová, A., Grófová, M., Matoŝka, J., Doré, J.F., Bertrand, S., Blaŝko, M., Vaheri, A. Cancer Res. (1989) [Pubmed]
  2. Polymyxin B-conjugated alpha 2-macroglobulin as an adjunctive therapy to sepsis: Modes of action and impact on lethality. Birkenmeier, G., Nicklisch, S., Pockelt, C., Mossie, A., Steger, V., Gläser, C., Hauschildt, S., Usbeck, E., Huse, K., Sack, U., Bauer, M., Schäfer, A. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  3. Relationship between the functional status of the reticuloendothelial system and the outcome of experimentally induced pancreatitis in young mice. Adham, N.F., Song, M.K., Haberfelde, G.C. Gastroenterology (1983) [Pubmed]
  4. Amantadine and dansylcadaverine inhibit vesicular stomatitis virus uptake and receptor-mediated endocytosis of alpha 2-macroglobulin. Schlegel, R., Dickson, R.B., Willingham, M.C., Pastan, I.H. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  5. Detection of alpha 2-macroglobulin, alpha 1-protease inhibitor, and neutral protease-antiprotease complexes within liver granulomas of Schistosoma mansoni-infected mice. Truden, J.L., Boros, D.L. Am. J. Pathol. (1988) [Pubmed]
  6. Rapid acidification of endocytic vesicles containing alpha 2-macroglobulin. Tycko, B., Maxfield, F.R. Cell (1982) [Pubmed]
  7. The receptosome: an intermediate organelle of receptor mediated endocytosis in cultured fibroblasts. Willingham, M.C., Pastan, I. Cell (1980) [Pubmed]
  8. Topographical distribution of coated pits. Pfeiffer, J.R., Oliver, J.M., Berlin, R.D. Nature (1980) [Pubmed]
  9. Receptors for maleylated proteins regulate secretion of neutral proteases by murine macrophages. Johnson, W.J., Pizzo, S.V., Imber, M.J., Adams, D.O. Science (1982) [Pubmed]
  10. An alpha 2-macroglobulin receptor-dependent mechanism for the plasma clearance of transforming growth factor-beta 1 in mice. LaMarre, J., Hayes, M.A., Wollenberg, G.K., Hussaini, I., Hall, S.W., Gonias, S.L. J. Clin. Invest. (1991) [Pubmed]
  11. A murine model for the study of mycotic mastitis. Guhad, F.A., Jensen, H.E., Aalbaek, B., Rycroft, A., Hau, J. J. Comp. Pathol. (1995) [Pubmed]
  12. The role of cAMP-dependent signaling in receptor-recognized forms of alpha 2-macroglobulin-induced cellular proliferation. Misra, U.K., Akabani, G., Pizzo, S.V. J. Biol. Chem. (2002) [Pubmed]
  13. Targeted inactivation of the mouse alpha 2-macroglobulin gene. Umans, L., Serneels, L., Overbergh, L., Lorent, K., Van Leuven, F., Van den Berghe, H. J. Biol. Chem. (1995) [Pubmed]
  14. Assignment of mouse alpha-2-macroglobulin gene to chromosome 6 band F1-G3. Hilliker, C., Overbergh, L., Petit, P., Van Leuven, F., Van den Berghe, H. Mamm. Genome (1992) [Pubmed]
  15. alpha 2-macroglobulin adsorbed to colloidal gold: a new probe in the study of receptor-mediated endocytosis. Dickson, R.B., Willingham, M.C., Pastan, I. J. Cell Biol. (1981) [Pubmed]
  16. Molecular characterization of the murinoglobulins. Overbergh, L., Torrekens, S., Van Leuven, F., Van den Berghe, H. J. Biol. Chem. (1991) [Pubmed]
  17. Alpha-2 macroglobulin controls trophoblast positioning in mouse implantation sites. Esadeg, S., He, H., Pijnenborg, R., Van Leuven, F., Croy, B.A. Placenta (2003) [Pubmed]
  18. The relationship between low density lipoprotein-related protein/alpha 2-macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling receptor. Misra, U.K., Chu, C.T., Gawdi, G., Pizzo, S.V. J. Biol. Chem. (1994) [Pubmed]
  19. Ligation of cell surface-associated glucose-regulated protein 78 by receptor-recognized forms of alpha 2-macroglobulin: activation of p21-activated protein kinase-2-dependent signaling in murine peritoneal macrophages. Misra, U.K., Sharma, T., Pizzo, S.V. J. Immunol. (2005) [Pubmed]
  20. alpha 2 Macroglobulin binding to the plasma membrane of cultured fibroblasts. Diffuse binding followed by clustering in coated regions. Willingham, M.C., Maxfield, F.R., Pastan, I.H. J. Cell Biol. (1979) [Pubmed]
  21. Analysis of the binding of pro-urokinase and urokinase-plasminogen activator inhibitor-1 complex to the low density lipoprotein receptor-related protein using a Fab fragment selected from a phage-displayed Fab library. Horn, I.R., Moestrup, S.K., van den Berg, B.M., Pannekoek, H., Nielsen, M.S., van Zonneveld, A.J. J. Biol. Chem. (1995) [Pubmed]
  22. Inhibition of platelet-derived growth factor-BB-induced fibroblast proliferation by plasmin-activated alpha 2-macroglobulin is mediated via an alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein-dependent mechanism. Bonner, J.C., Badgett, A., Hoffman, M., Lindroos, P.M. J. Biol. Chem. (1995) [Pubmed]
  23. The exposure of murine macrophages to alpha 2-macroglobulin 'fast' forms results in the rapid secretion of eicosanoids. Uhing, R.J., Martenson, C.H., Rubenstein, D.S., Hollenbach, P.W., Pizzo, S.V. Biochim. Biophys. Acta (1991) [Pubmed]
  24. Weak bases and ionophores rapidly and reversibly raise the pH of endocytic vesicles in cultured mouse fibroblasts. Maxfield, F.R. J. Cell Biol. (1982) [Pubmed]
  25. Receptor-mediated antigen delivery into macrophages. Complexing antigen to alpha 2-macroglobulin enhances presentation to T cells. Chu, C.T., Pizzo, S.V. J. Immunol. (1993) [Pubmed]
  26. Regulation of cytosolic phospholipase A2 activity in macrophages stimulated with receptor-recognized forms of alpha 2-macroglobulin: role in mitogenesis and cell proliferation. Misra, U.K., Pizzo, S.V. J. Biol. Chem. (2002) [Pubmed]
  27. Mouse macrophage elastase. Purification and characterization as a metalloproteinase. Banda, M.J., Werb, Z. Biochem. J. (1981) [Pubmed]
  28. Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor on murine peritoneal macrophages mediates the binding and catabolism of low-density lipoprotein. Wu, S.M., Pizzo, S.V. Arch. Biochem. Biophys. (1996) [Pubmed]
  29. Expression in mouse embryos and in adult mouse brain of three members of the amyloid precursor protein family, of the alpha-2-macroglobulin receptor/low density lipoprotein receptor-related protein and of its ligands apolipoprotein E, lipoprotein lipase, alpha-2-macroglobulin and the 40,000 molecular weight receptor-associated protein. Lorent, K., Overbergh, L., Moechars, D., De Strooper, B., Van Leuven, F., Van den Berghe, H. Neuroscience (1995) [Pubmed]
  30. The primary sequence and the subunit structure of mouse alpha-2-macroglobulin, deduced from protein sequencing of the isolated subunits and from molecular cloning of the cDNA. van Leuven, F., Torrekens, S., Overbergh, L., Lorent, K., de Strooper, B., van den Berghe, H. Eur. J. Biochem. (1992) [Pubmed]
  31. Mapping of structure-function relationships in proteins with a panel of monoclonal antibodies. A study on human alpha 2 macroglobulin. Van Leuven, F., Marynen, P., Cassiman, J.J., Van den Berghe, H. J. Immunol. Methods (1988) [Pubmed]
  32. Isolation and characterization of alpha 2-macroglobulin-protease complexes from purified mouse mammary tumor virus and culture supernatants from virus-infected cell lines. Menéndez-Arias, L., Risco, C., Oroszlan, S. J. Biol. Chem. (1992) [Pubmed]
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