Disease relevance of A2m

• Clonal variation in the production of tumor-associated alpha 2-macroglobulin in a malignant human melanoma and association with growth stimulation [1].
• Polymyxin B-conjugated alpha 2-macroglobulin as an adjunctive therapy to sepsis: Modes of action and impact on lethality [2].
• Stimulating the reticuloendothelial system in 4-wk-old mice significantly (a) decreased the mortality rate; (b) lessened the drop in the plasma content of both alpha 2-macroglobulin and alpha 1-antitrypsin; and (c) decreased the severity of pancreatitis noted microscopically [3].
• Amantadine and dansylcadaverine inhibit vesicular stomatitis virus uptake and receptor-mediated endocytosis of alpha 2-macroglobulin [4].
• To determine the cause of diminished neutral protease activity, the authors determined levels of the antiprotease/alpha 2-macroglobulin (alpha 2M) and alpha 1-protease inhibitor (alpha 1Pi) in extracts or secretions of liver granulomas of infected mice [5].

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

• The role of cAMP-dependent signaling in receptor-recognized forms of alpha 2-macroglobulin-induced cellular proliferation [12].
• Liver alpha 2-macroglobulin mRNA and plasma protein was absent in homozygotes and reduced to 50% in heterozygotes. alpha 2-Macroglobulin-deficient mice were viable and produced normally sized litters with normal sex ratio over 3 generations [13].
• Assignment of mouse alpha-2-macroglobulin gene to chromosome 6 band F1-G3 [14].
• alpha 2-macroglobulin adsorbed to colloidal gold: a new probe in the study of receptor-mediated endocytosis [15].
• To retrieve related sequences we screened a mouse liver cDNA library with human alpha 2M cDNA [16].

Anatomical context of A2m

• Alpha-2 macroglobulin controls trophoblast positioning in mouse implantation sites [17].
• alpha 2-Macroglobulin (alpha 2M)-methylamine binding to macrophages appears to involve two receptors [18].
• 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 [19].
• The mouse alpha 2-macroglobulin gene was inactivated in embryonic stem cells by homologous recombination [13].
• alpha 2 Macroglobulin binding to the plasma membrane of cultured fibroblasts. Diffuse binding followed by clustering in coated regions [20].

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

• Regulation of cytosolic phospholipase A2 activity in macrophages stimulated with receptor-recognized forms of alpha 2-macroglobulin: role in mitogenesis and cell proliferation [26].
• Macrophage elastase was inhibited by alpha 2-macroglobulin, but not by alpha 1-proteinase inhibitor [27].

Other interactions of A2m

• Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor on murine peritoneal macrophages mediates the binding and catabolism of low-density lipoprotein [28].
• Regulation of murinoglobulin mRNA expression during pregnancy was analyzed as a possible back-up mechanism for the deficiency in alpha 2-macroglobulin [13].
• Our results provide evidence for the presence of an interaction site for pro-u-PA localized in the second cluster of cysteine-rich repeats that is unrelated to the t-PA.PAI-1 or methylamine-activated alpha 2-macroglobulin interaction sites [21].
• Receptor-associated protein, which binds to LRP but not the alpha 2M signaling receptor, blocks the lactoferrin signal but has no effect on alpha 2M-methylamine signaling [18].
• Among adult mouse tissues, the genes investigated were expressed very prominently in brain, except for lipoprotein lipase and for the complete absence of alpha-2-macroglobulin messenger RNA [29].

Analytical, diagnostic and therapeutic context of A2m

• 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 [30].
• Using transmission electron microscopy, we have studied the interaction of alpha 2 macroglobulin (alpha 2 M) with the surface of cultured fibroblasts [20].
• Immunofluorescence staining of cultured HMB-2 cells suggested that the cell population is heterogeneous with respect to alpha 2-M production [1].
• Finally, Western blotting was used as a first approximate mapping of the epitope relative to the internal thiolesters by exploiting the heat-induced fragmentation of alpha 2M at this site [31].
• Therefore, the alpha 2-macroglobulin present in the cell culture medium is able to bind proteases, forming high molecular weight complexes, which are active against peptide substrates, copurify with the virus and are responsible for the nonviral proteolytic activities found in the purified virus [32].

References