alpha 2 macroglobulin


Gene Symbol: alpha 2 macroglobulin
Description: alpha-2-macroglobulin
Alias: A2MD, CPAMD5, FWP007, S863-7, alpha-2-macroglobulin, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5, alpha-2-M
Species: human
Products:     alpha 2 macroglobulin

Top Publications

  1. Kuno K, Terashima Y, Matsushima K. ADAMTS-1 is an active metalloproteinase associated with the extracellular matrix. J Biol Chem. 1999;274:18821-6 pubmed
    ..Consequently, ADAMTS-1 is an active metalloprotease that is associated with the extracellular matrix. This study strongly suggests that ADAMTS-1 may play a role in the inflammatory process through its protease activity. ..
  2. Misra U, Gonzalez Gronow M, Gawdi G, Hart J, Johnson C, Pizzo S. The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction. J Biol Chem. 2002;277:42082-7 pubmed
  3. Jensen P, Humle Jørgensen S, Datta P, Sørensen P. Significantly increased fractions of transformed to total alpha2-macroglobulin concentrations in plasma from patients with multiple sclerosis. Biochim Biophys Acta. 2004;1690:203-7 pubmed
    ..The results suggest an important involvement of alpha2M in regulation of increased proteolytic activity occurring in MS disease. ..
  4. Misra U, Deedwania R, Pizzo S. Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. J Biol Chem. 2005;280:26278-86 pubmed
    ..These studies suggest a mechanism by which alpha2M* enhances the metastatic potential of these cells. ..
  5. Wilson M, Yerbury J, Poon S. Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity. Mol Biosyst. 2008;4:42-52 pubmed
    ..Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. ..
  6. French K, Yerbury J, Wilson M. Protease activation of alpha2-macroglobulin modulates a chaperone-like action with broad specificity. Biochemistry. 2008;47:1176-85 pubmed publisher
  7. Yerbury J, Kumita J, Meehan S, Dobson C, Wilson M. alpha2-Macroglobulin and haptoglobin suppress amyloid formation by interacting with prefibrillar protein species. J Biol Chem. 2009;284:4246-54 pubmed publisher
    ..These findings suggest that both alpha(2)M and Hp are likely to play an important role in controlling the inappropriate aggregation of proteins in the extracellular environment. ..
  8. Borth W. Alpha 2-macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J. 1992;6:3345-53 pubmed
  9. Chen Y, Xu K, Li J, Wang X, Ye Y, Qi P. Molecular characterization of complement component 3 (C3) in Mytilus coruscus improves our understanding of bivalve complement system. Fish Shellfish Immunol. 2018;76:41-47 pubmed publisher
    ..Taken together, these results show that C3 may play an essential role in the immune defense of M. coruscus. The present data therefore provide a more detailed insight into the functional activities of the bivalve complement system. ..

More Information

Publications124 found, 100 shown here

  1. Arnold J, Wallis R, Willis A, Harvey D, Royle L, Dwek R, et al. Interaction of mannan binding lectin with alpha2 macroglobulin via exposed oligomannose glycans: a conserved feature of the thiol ester protein family?. J Biol Chem. 2006;281:6955-63 pubmed
    ..Binding would lead to opsonization or activation of enzyme systems such as complement. ..
  2. Seriramalu R, Pang W, Jayapalan J, Mohamed E, Abdul Rahman P, Bustam A, et al. Application of champedak mannose-binding lectin in the glycoproteomic profiling of serum samples unmasks reduced expression of alpha-2 macroglobulin and complement factor B in patients with nasopharyngeal carcinoma. Electrophoresis. 2010;31:2388-95 pubmed publisher
    ..Together with other acute-phase response proteins that were previously reported to be altered in expression in NPC patients, AMG and CFB may serve as useful complementary biomarkers for NPC. ..
  3. Choi G, Kim J, Shin Y, Ye Y, Kim S, Park H. Eosinophil activation and novel mediators in the aspirin-induced nasal response in AERD. Clin Exp Allergy. 2013;43:730-40 pubmed publisher
    ..Eosinophil activation occurred in early and late responses after L-ASA NPT in upper airway mucosa of AERD patients, where ApoA1, ?2M and CP as well as CysLT may be involved in eosinophilic inflammation. ..
  4. Kelly B, Lautenbach E, Nachamkin I, Coffin S, Gerber J, Fuchs B, et al. Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis. Diagn Microbiol Infect Dis. 2016;85:109-15 pubmed publisher
    ..The combination of A2M and PCT discriminated bacterial sepsis from other SIRS among SICU patients with suspected sepsis. ..
  5. Zhao K, Murray E, Murray S. HK2 Proximal Tubule Epithelial Cells Synthesize and Secrete Plasma Proteins Predominantly Through the Apical Surface. J Cell Biochem. 2017;118:924-933 pubmed publisher
    ..J. Cell. Biochem. 118: 924-933, 2017. © 2016 Wiley Periodicals, Inc. ..
  6. Sottrup Jensen L, Stepanik T, Kristensen T, Wierzbicki D, Jones C, Lønblad P, et al. Primary structure of human alpha 2-macroglobulin. V. The complete structure. J Biol Chem. 1984;259:8318-27 pubmed
    ..The properties of alpha 2-macroglobulin are discussed within the context of proteolytically regulated systems with particular reference to the complement components C3 and C4. ..
  7. McElhinney B, Ardill J, Caldwell C, Lloyd F, McClure N. Ovarian hyperstimulation syndrome and assisted reproductive technologies: why some and not others?. Hum Reprod. 2002;17:1548-53 pubmed
    ..alpha(2)M measurements may help to differentiate those for whom it is safe to proceed with embryo transfer from those for whom it is not, because of the risk of OHSS. ..
  8. Arandjelovic S, Hall B, Gonias S. Mutation of lysine 1370 in full-length human alpha2-macroglobulin blocks binding to the low density lipoprotein receptor-related protein-1. Arch Biochem Biophys. 2005;438:29-35 pubmed
    ..7 cells was blocked by receptor-associated protein, indicating an essential role for LRP-1. These studies demonstrate that a single mutation in full-length r(alpha)2M is sufficient to block binding to LRP-1. ..
  9. Narita K, Sasamoto S, Koizumi S, Okazaki S, Nakamura H, Inoue T, et al. TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. FASEB J. 2015;29:2247-59 pubmed publisher
    ..Overall, this study demonstrated a novel physiologic function of TRPV4 in the regulation of BCSFB permeability. ..
  10. Ferrier G, Kim S, Kaddis C, Loo J, Ann Zimmer C, Zimmer R. MULTIFUNCin: A Multifunctional Protein Cue Induces Habitat Selection by, and Predation on, Barnacles. Integr Comp Biol. 2016;56:901-913 pubmed
    ..As a multifunctional protein cue, MULTIFUNCin provides valuable sensory information, conveys different messages to different species, and drives complex biotic interactions. ..
  11. Bísaro de Lorenc L, Ramos A, Sanchez M, Montenegro R, Chiabrando G. Structural evaluation of plasma alpha2-macroglobulin in acute pancreatitis. Clin Chem Lab Med. 2005;43:1183-9 pubmed
    ..Finally, the structural evaluation of plasma alpha2-macroglobulin could be used as a prognostic marker of the severity of acute pancreatitis. ..
  12. Bonacci G, Cáceres L, Sanchez M, Chiabrando G. Activated alpha(2)-macroglobulin induces cell proliferation and mitogen-activated protein kinase activation by LRP-1 in the J774 macrophage-derived cell line. Arch Biochem Biophys. 2007;460:100-6 pubmed
    ..These results suggest that alpha(2)M*/LRP-1 interaction constitutes a key role in the macrophage functioning during inflammation and cancer. ..
  13. Zouhir S, Robert Genthon M, Trindade D, Job V, Nedeljkovic M, Breyton C, et al. Assembly of an atypical ?-macroglobulin complex from Pseudomonas aeruginosa. Sci Rep. 2018;8:527 pubmed publisher
  14. Riely G, Rachmilewitz J, Koo P, Tykocinski M. alpha2-macroglobulin modulates the immunoregulatory function of the lipocalin placental protein 14. Biochem J. 2000;351 Pt 2:503-8 pubmed
    ..Moreover, this represents the first documented interaction between the protein carrier alpha(2)M and a lipocalin protein. ..
  15. Adler V, Davidowitz E, Tamburi P, Rojas P, Grossman A. Alpha2-macroglobulin is a potential facilitator of prion protein transformation. Amyloid. 2007;14:1-10 pubmed
    ..Purification of proteins from this fraction led to the identification of alpha2-macroglobulin as an active component suggesting that it may facilitate conformational changes in prion protein in spontaneous forms of prion disease. ..
  16. van Esch S, van Diepen A, Struijk D, Krediet R. The Mutual Relationship Between Peritonitis and Peritoneal Transport. Perit Dial Int. 2016;36:33-42 pubmed publisher
    ..This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. ..
  17. Hu C, Sung S, Liu H, Hsu W, Lee L, Lee C, et al. Genetic risk factors of sporadic Alzheimer's disease among Chinese in Taiwan. J Neurol Sci. 2000;181:127-31 pubmed
    ..The other candidate genes in this study were not associated with the occurrence of AD. In addition, there are no gene-gene interactions. ..
  18. Nacmias B, Tedde A, Cellini E, Forleo P, Orlacchio A, Guarnieri B, et al. Alpha2-macroglobulin polymorphisms in Italian sporadic and familial Alzheimer's disease. Neurosci Lett. 2001;299:9-12 pubmed
    ..Our data do not confirm these associations, in particular we found a significant decrease of the deletion allele in AD with respect to controls. Our data do not support a role for the A2M gene as genetic risk factor for AD. ..
  19. Zhang Y, Ge G, Greenspan D. Inhibition of bone morphogenetic protein 1 by native and altered forms of alpha2-macroglobulin. J Biol Chem. 2006;281:39096-104 pubmed
    ..These findings suggest possible therapeutic interventions involving ectopic expression of modified versions of alpha(2)-macroglobulin in the treatment of fibrotic conditions. ..
  20. Li X, Ye L, Ge Y, Yuan K, Zhang Y, Liang Y, et al. In utero perfluorooctane sulfonate exposure causes low body weights of fetal rats: A mechanism study. Placenta. 2016;39:125-33 pubmed publisher
    ..PFOS exposure may alter placental development and function, causing intrauterine growth restriction via inhibiting placental 11?-hydroxysteroid dehydrogenase 2. ..
  21. Nicosia F, Alberici A, Benussi L, Gasparini L, Ghidoni R, Mazzoli F, et al. Analysis of alpha-2-macroglobulin-2 allele as a risk factor in Alzheimer's disease. Dement Geriatr Cogn Disord. 2001;12:305-8 pubmed
    ..89) or genotype frequency (p = 0.97) in the two different clinical series and in control subjects. The frequencies were not significantly different after stratification by APOE epsilon4 status. ..
  22. Huang M, Austin C, Sari M, Rahmanto Y, Ponka P, Vyoral D, et al. Hepcidin bound to ?2-macroglobulin reduces ferroportin-1 expression and enhances its activity at reducing serum iron levels. J Biol Chem. 2013;288:25450-65 pubmed publisher
    ..A model is proposed that suggests that unlike proteases, which are irreversibly bound to activated ?2M, hepcidin remains labile and available to down-regulate Fpn1. ..
  23. Mettenburg J, Webb D, Gonias S. Distinct binding sites in the structure of alpha 2-macroglobulin mediate the interaction with beta-amyloid peptide and growth factors. J Biol Chem. 2002;277:13338-45 pubmed
    ..These studies suggest a model in which alpha(2)M has three protein interaction sites with distinct specificities, mediating the interaction with Abeta, growth factors, and LRP. ..
  24. Birkenmeier G, Muller R, Huse K, Forberg J, Glaser C, Hedrich H, et al. Human alpha2-macroglobulin: genotype-phenotype relation. Exp Neurol. 2003;184:153-61 pubmed
    ..However, it can be speculated that the observed general age-related alpha2-M deficiency may lead to accelerated accumulation of amyloid-beta, which might be relevant to AD pathology. ..
  25. Tayade C, Esadeg S, Fang Y, Croy B. Functions of alpha 2 macroglobulins in pregnancy. Mol Cell Endocrinol. 2005;245:60-6 pubmed
    ..Here, we review the A2M gene families of mice and humans, the predicted structural relationships between A2M and its pregnancy induced forms and the postulated roles for this gene family in normal pregnancy. ..
  26. Ozawa D, Hasegawa K, Lee Y, Sakurai K, Yanagi K, Ookoshi T, et al. Inhibition of beta2-microglobulin amyloid fibril formation by alpha2-macroglobulin. J Biol Chem. 2011;286:9668-76 pubmed publisher
  27. Shemesh C, Yu R, Gaus H, Seth P, Swayze E, Bennett F, et al. Pharmacokinetic and Pharmacodynamic Investigations of ION-353382, a Model Antisense Oligonucleotide: Using Alpha-2-Macroglobulin and Murinoglobulin Double-Knockout Mice. Nucleic Acid Ther. 2016;26:223-35 pubmed publisher
    ..Binding to A2M could mediate ASOs to nonproductive compartments, and thus, decreased binding of ASOs to A2M could potentially improve ASO pharmacology. ..
  28. McIlroy S, Dynan K, Vahidassr D, Lawson J, Patterson C, Passmore P. Common polymorphisms in LRP and A2M do not affect genetic risk for Alzheimer disease in Northern Ireland. Am J Med Genet. 2001;105:502-6 pubmed
    ..The results from this study indicate that polymorphisms in LRP and A2M are not associated with increased risk for AD in Northern Ireland. ..
  29. Zappia M, Cittadella R, Manna I, Nicoletti G, Andreoli V, Bonavita S, et al. Genetic association of alpha2-macroglobulin polymorphisms with AD in southern Italy. Neurology. 2002;59:756-8 pubmed
    ..Moreover, subjects carrying the A2M genotype I/I-Val/Val had a threefold increase of risk for AD. These data support a population-based susceptibility for AD linked to A2M polymorphisms. ..
  30. Chhina S, Rathore A, Juneja S. Alpha-2-Macroglobulin Levels in Gingival Crevicular Fluid Pre- and Post-scaling and Root Planing with Adjunctive Tetracycline Fibers in Chronic Periodontitis: A Randomized Controlled Trial. J Contemp Dent Pract. 2015;16:474-8 pubmed
    ..001). Clinical and biochemical variables showed a more favorable outcome when SRP was combined with LDD of tetracycline fibers in management of patients suffering from chronic periodontitis. ..
  31. Lu Y, Chen X, Yin Z, Zhu S, Wu D, Chen X. Screening for potential serum biomarkers in rat mesangial proliferative nephritis. Proteomics. 2016;16:1015-22 pubmed publisher
    ..Overall, this study explored a group of candidate biomarkers of mesangial proliferation inducing kidney injury, to provide the basis of an assessment model for MesPGN in the future. ..
  32. Shibata M, Sakai H, Sakai E, Okamoto K, Nishishita K, Yasuda Y, et al. Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E. Eur J Biochem. 2003;270:1189-98 pubmed
    ..These results suggest the possible involvement of cathepsin E in disruption of the structural and functional integrity of alpha 2M in the endolysosome system. ..
  33. Cai L, Tang G, Chen L, Zhang B, Jiang S, Ren D. Genetic studies of A2M and BACE1 genes in Chinese Han Alzheimer's disease patients. Neuroreport. 2005;16:1023-6 pubmed
    ..Through combination-analysis of the data about the A2M-I/D and the A2M-Ile1000Val variants, the A2M gene was suggested to be associated with Alzheimer's disease. ..
  34. Yuan Q, Wang F, Xue S, Jia J. Association of polymorphisms in the LRP1 and A2M genes with Alzheimer's disease in the northern Chinese Han population. J Clin Neurosci. 2013;20:253-6 pubmed publisher
    ..001), but no interaction between LRP1 and A2M genotypes. Our results suggest that the T allele of the LRP1 C766T polymorphism is associated with a decreased risk of SAD in APOE ?4 carriers from the Northern Han Chinese population. ..
  35. Carli A, Harvey E, Azeddine B, Gao C, Li Y, Li A, et al. Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis incidence in a rat model. J Orthop Res. 2017;35:1183-1194 pubmed publisher
    ..2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1183-1194, 2017. ..
  36. Blacker D, Wilcox M, Laird N, Rodes L, Horvath S, Go R, et al. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet. 1998;19:357-60 pubmed
  37. Gonzalez P, Alvarez R, Reguero J, Batalla A, Alvarez V, Cortina A, et al. Variation in the lipoprotein receptor-related protein, alpha2-macroglobulin and lipoprotein receptor-associated protein genes in relation to plasma lipid levels and risk of early myocardial infarction. Coron Artery Dis. 2002;13:251-4 pubmed
    ..0065; odds ratio = 2.18, 95% confidence intervals = 1.22-3.90). According to our data, the variation at the LRPAP1 gene could contribute to the risk of developing an early episode of MI. ..
  38. Styczynska M, Religa D, Pfeffer A, Luczywek E, Wasiak B, Styczynski G, et al. Simultaneous analysis of five genetic risk factors in Polish patients with Alzheimer's disease. Neurosci Lett. 2003;344:99-102 pubmed
    ..Our results suggest that the APOE epsilon 4 allele is the only known genetic risk factor for late-onset, sporadic AD. ..
  39. Nascimento A, Cajazeiras J, Nascimento K, Nogueira S, Sousa B, Teixeira E, et al. Expression, purification and structural analysis of recombinant rBdh-2His?, a spermadhesin from buck (Capra hircus) seminal plasma. Reprod Fertil Dev. 2012;24:580-7 pubmed publisher
    ..The structure of rBdh-2His? remained stable up to 35°C. However, significant structural changes were observed at temperatures higher than 40 °C related to a distortion of the CD spectrum. ..
  40. Thieme R, Kurz S, Kolb M, Debebe T, Holtze S, Morhart M, et al. Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma. PLoS ONE. 2015;10:e0130470 pubmed publisher
    ..This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the anti-aging mechanisms in the NMR. ..
  41. Zhang Y, Wei X, Browning S, Scuderi G, Hanna L, Wei L. Targeted designed variants of alpha-2-macroglobulin (A2M) attenuate cartilage degeneration in a rat model of osteoarthritis induced by anterior cruciate ligament transection. Arthritis Res Ther. 2017;19:175 pubmed publisher
    ..The targeted variants of A2M have a chondroprotective effect similar to wt-A2M. However, A2M-108 variant has enhanced function to attenuate cartilage degeneration compared with wt-A2M. ..
  42. Cattaneo A, Cattane N, Malpighi C, Czamara D, Suarez A, Mariani N, et al. FoxO1, A2M, and TGF-β1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses. Mol Psychiatry. 2018;: pubmed publisher
    ..We therefore provide a successful 'hypothesis-free' approach for the identification and prioritization of candidate genes for GxE interaction studies that can be investigated in GWAS datasets. ..
  43. Falkenberg C, Grubb A, Akerstrom B. Isolation of rat serum alpha 1-microglobulin. Identification of a complex with alpha 1-inhibitor-3, a rat alpha 2-macroglobulin homologue. J Biol Chem. 1990;265:16150-7 pubmed
    ..alpha 1-m complex and free alpha 1-m were determined as 0.16 and 0.010 g/liter, respectively. Thus, alpha 1I3.alpha 1-m constitutes 1-3% of the total alpha 1I3 in rat serum (w/w) and approximately 60% of the total alpha 1-m. ..
  44. Møllgård K, Dziegielewska K, Saunders N, Zakut H, Soreq H. Synthesis and localization of plasma proteins in the developing human brain. Integrity of the fetal blood-brain barrier to endogenous proteins of hepatic origin. Dev Biol. 1988;128:207-21 pubmed
  45. Sun Y, Shi J, Zhang S, Tang M, Liu X, Wang Y, et al. [No evidence for genetic association between alpha-2 macroglobulin I1000V polymorphism and sporadic Alzheimer's disease in two independent Chinese populations]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005;22:174-9 pubmed
    ..The results of this study revealed no association between the I1000V polymorphism of A2M and Chinese sporadic AD in Guangzhou and Chengdu. ..
  46. Meier U, Billich A, Mann K, Schramm H, Schramm W. alpha 2-Macroglobulin is cleaved by HIV-1 protease in the bait region but not in the C-terminal inter-domain region. Biol Chem Hoppe Seyler. 1991;372:1051-6 pubmed
    ..In AIDS, therefore, HIV protease from infected cells in unlikely to interfere with receptor-binding of alpha 2-macroglobulin. ..
  47. Wang X, Luedecking E, Minster R, Ganguli M, Dekosky S, Kamboh M. Lack of association between alpha2-macroglobulin polymorphisms and Alzheimer's disease. Hum Genet. 2001;108:105-8 pubmed
    ..In conclusion, we observed no association between either the intronic deletion polymorphism or the Ile1000Val polymorphism of A2M and AD in our case-control cohort. ..
  48. Toombs C. Alfimeprase: pharmacology of a novel fibrinolytic metalloproteinase for thrombolysis. Haemostasis. 2001;31:141-7 pubmed
    ..As a result, systemic bleeding complications have been greatly reduced due to the inhibitory effects of alpha(2)-macroglobulin. This article reviews the biochemical in vitro and in vivo characteristics of this novel acting thrombolytic. ..
  49. Zhang P, Yang Z, Wan C, Zheng W, Zhang C, Li S, et al. Neither the tumor necrosis factor alpha-308 A/G polymorphism nor the alpha2-macroglobulin polymorphism was associated with late-onset Alzheimer's disease in the Chinese population. Yi Chuan Xue Bao. 2004;31:1-6 pubmed
    ..01) neither the frequencies of genotypes nor alleles of the TNF alpha-308 A/G and A2M polymorphisms were significantly different between AD and controls,suggesting the two polymorphisms were not risk factors to LOAD in Chinese. ..
  50. Lin V, Wang S, Boetticher N, Vazquez D, Saboorian H, McConnell J, et al. Alpha(2) macroglobulin, a PSA binding protein, is expressed in human prostate stroma. Prostate. 2005;63:299-308 pubmed
    ..Considering the unique features of its protein binding and targeting properties, alpha(2)-M expressed in the prostate may play an important role in regulating benign and malignant prostatic growth. ..
  51. Xiao Y, Zhang B. [Association of the polymorphism in alpha-2 macroglobulin gene with essential tremor and Parkinson's disease]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006;23:84-5 pubmed
    ..2) There might be no association of polymorphism at the site of I/D with PD and ET in North China. ..
  52. Shiu Y, Chiu K, Huynh T, Liu P, Liu C. Plasma immune protein analysis in the orange-spotted grouper Epinephelus coioides: Evidence for altered expressions of immune factors associated with a choline-supplemented diet. Fish Shellfish Immunol. 2017;65:235-243 pubmed publisher
  53. Sauer H, Ravindran F, Beldoch M, Sharifpanah F, Jedelská J, Strehlow B, et al. ?2-Macroglobulin enhances vasculogenesis/angiogenesis of mouse embryonic stem cells by stimulation of nitric oxide generation and induction of fibroblast growth factor-2 expression. Stem Cells Dev. 2013;22:1443-54 pubmed publisher
    ..In conclusion, ?2M stimulates endothelial and early cardiac, but not smooth muscle differentiation of ES cells through generation of NO, activation of ERK1/2 as well as PI3K, and induction of FGF-2 expression. ..
  54. Westwood S, Leoni E, Hye A, Lynham S, Khondoker M, Ashton N, et al. Blood-Based Biomarker Candidates of Cerebral Amyloid Using PiB PET in Non-Demented Elderly. J Alzheimers Dis. 2016;52:561-72 pubmed publisher
    ..As in previous studies, acute phase reactants and inflammatory markers dominate this signature. ..
  55. Jensen P, Sottrup Jensen L. Primary structure of human alpha 2-macroglobulin. Complete disulfide bridge assignment and localization of two interchain bridges in the dimeric proteinase binding unit. J Biol Chem. 1986;261:15863-9 pubmed
    ..The disulfide bridge pattern of alpha 2M has been completed by showing that the alpha 2M subunit contains 11 intrachain bridges, including a bridge connecting Cys447 with Cys540. ..
  56. Kan C, Solomon E, Belt K, Chain A, Hiorns L, Fey G. Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus. Proc Natl Acad Sci U S A. 1985;82:2282-6 pubmed
    ..The alpha 2M locus was assigned to human chromosome 12 by Southern blot analysis with DNA from a panel of mouse/human somatic cell hybrids, using alpha 2M cDNA as a hybridization probe. ..
  57. Gustavsson E, Ohlsson K, Olsson A. Interaction between human pancreatic elastase and plasma protease inhibitors. Hoppe Seylers Z Physiol Chem. 1980;361:169-76 pubmed
    ..The elastase bound by alpha 2-macroglobulin retains its activity against low molecular weight substrates, while that bound by alpha 1-antitrypsin is enzymologically inactive. ..
  58. Sottrup Jensen L, Lønblad P, Stepanik T, Petersen T, Magnusson S, Jornvall H. Primary structure of the 'bait' region for proteinases in alpha 2-macroglobulin. Nature of the complex. FEBS Lett. 1981;127:167-73 pubmed
  59. Krimbou L, Tremblay M, Davignon J, Cohn J. Association of apolipoprotein E with alpha2-macroglobulin in human plasma. J Lipid Res. 1998;39:2373-86 pubmed
  60. Huang W, Dolmer K, Liao X, Gettins P. Localization of basic residues required for receptor binding to the single alpha-helix of the receptor binding domain of human alpha2-macroglobulin. Protein Sci. 1998;7:2602-12 pubmed
    ..Secondary structure predictions of other alpha-macroglobulins show the conservation of this alpha-helix and suggest an important role for this helix and for basic residues within it for receptor binding. ..
  61. Zill P, Burger K, Behrens S, Hampel H, Padberg F, Boetsch T, et al. Polymorphisms in the alpha-2 macroglobulin gene in psychogeriatric patients. Neurosci Lett. 2000;294:69-72 pubmed
  62. Pang C, Baum L, Lam D. Hunting for disease genes in multi-functional diseases. Clin Chem Lab Med. 2000;38:819-25 pubmed
    ..New information from the Human Genome Project and advancements in technologies will aid the search for and confirm identification of disease genes despite such challenges...
  63. Ki C, Na D, Kim H, Kim J. Alpha-1 antichymotrypsin and alpha-2 macroglobulin gene polymorphisms are not associated with Korean late-onset Alzheimer's disease. Neurosci Lett. 2001;302:69-72 pubmed
    ..Our results do not support previously reported association of ACT and A2M with LOAD, at least in Korean population. ..
  64. Teich N, Walther K, Bodeker H, MOssner J, Keim V. Relevance of variants in serum antiproteinases for the course of chronic pancreatitis. Scand J Gastroenterol. 2002;37:360-5 pubmed
    ..The A2M pentanucleotide deletion showed a homogenous distribution in patients and controls. Our study suggests a moderating, but not predominant, role of AAT variants in the course of chronic non-alcoholic pancreatitis. ..
  65. Scacchi R, Ruggeri M, Gambina G, Martini M, Corbo R. Alpha2-macroglobulin deletion polymorphism and plasma levels in late onset Alzheimer's disease. Clin Chem Lab Med. 2002;40:333-6 pubmed
  66. Anderson R, Cianciolo G, Kennedy M, Pizzo S. Alpha 2-macroglobulin binds CpG oligodeoxynucleotides and enhances their immunostimulatory properties by a receptor-dependent mechanism. J Leukoc Biol. 2008;83:381-92 pubmed
    ..CpG ODN bound to alpha 2M* are also protected from degradation by nucleases. This novel targeting technology may improve CpG ODN-based therapeutics by increasing efficacy at reduced doses, thus reducing side-effects and cost. ..
  67. Carter C. Interactions between the products of the Herpes simplex genome and Alzheimer's disease susceptibility genes: relevance to pathological-signalling cascades. Neurochem Int. 2008;52:920-34 pubmed publisher
  68. Tanskanen M, Peuralinna T, Polvikoski T, Notkola I, Sulkava R, Hardy J, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2008;40:232-9 pubmed publisher
    ..016). This population-based study shows that SSA is very common in old individuals, affecting one-quarter of people aged over 85 years. Myocardial infarctions and variation in the genes for alpha2M and tau may be associated with SSA. ..
  69. Moriya M, Ho Y, Grana A, Nguyen L, Alvarez A, Jamil R, et al. Copper is taken up efficiently from albumin and alpha2-macroglobulin by cultured human cells by more than one mechanism. Am J Physiol Cell Physiol. 2008;295:C708-21 pubmed publisher
  70. Flachsbart F, Caliebe A, Nothnagel M, Kleindorp R, Nikolaus S, Schreiber S, et al. Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals. Eur J Hum Genet. 2010;18:59-61 pubmed publisher
    ..Consequently, our data support an involvement of the suggested A2M risk haplotype in the pathogenesis of Alzheimer's disease and adds new evidence to the risk-allele depletion hypothesis. ..
  71. Song H, Jia L, Zuo X, Jia J. Association between haplotype -88G/25G in A2M with Alzheimer's disease. Neurosci Lett. 2010;479:143-5 pubmed publisher
    ..77, 95%CI 1.06-2.96, P=0.027). Our study supports that haplotype -88G/25G might play a protective role in the development of SAD, and the protective effects of -88G and 25G were independent of APOEvarepsilon4 allele. ..
  72. Murakami Y, Wada Y, Kobayashi H, Irie A, Hasegawa M, Yamanaka H, et al. Inhibition of Aeromonas sobria serine protease (ASP) by ?2-macroglobulin. Biol Chem. 2012;393:1193-200 pubmed publisher
    ..sobria infection sites. However, as shown by fluorescence correlation spectroscopy, slow ASP inhibition by ?2-MG in plasma may indicate insufficient ASP control in vivo. ..
  73. Sunderić M, Miljuš G, Nedić O. Interaction of insulin-like growth factor-binding protein 2 with ?2-macroglobulin in the circulation. Protein J. 2013;32:138-42 pubmed publisher
    ..Our results showed that IGFBP-2 associates with ?2-macroglobulin (?2M), a protease inhibitor. Formation of IGFBP-2/?2M complexes most likely contributes to the regulation of IGFBP-2 proteolysis and, thus, the activity of IGFs. ..
  74. Federici Canova D, Pavlov A, Norling L, Gobbetti T, Brunelleschi S, Le Fauder P, et al. Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response. J Control Release. 2015;217:284-92 pubmed publisher
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    ..Our findings suggest that SPARCL1 accelerates AD pathogenesis and thus link neuroinflammation with widespread changes in brain structure and function during aging...
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    ..Binding and cleavage were observed for both single-chain and two-chain forms of cathepsin B from human, ox, and pig livers, showing that all active forms of cathepsins B, H, and L are endopeptidases. ..
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    ..The physiological or pathophysiological role of this unique enzyme remains to be explored. ..
  78. Sayegh R, Awwad J, Maxwell C, Lessey B, Isaacson K. Alpha 2-macroglobulin production by the human endometrium. J Clin Endocrinol Metab. 1995;80:1021-6 pubmed
    ..This production is menstrual cycle dependent, with zonal differences in A2M expression within the endometrium, which may indicate a functional significance relevant to the process of implantation that merits further investigation. ..
  79. Birkenmeier G, Kämpfer I, Kratzsch J, Schellenberger W. Human leptin forms complexes with alpha 2-macroglobulin which are recognized by the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Eur J Endocrinol. 1998;139:224-30 pubmed
    ..Binding of leptin to transformed alpha2-M and its rapid clearance by the alpha2-M receptor may significantly influence the bioavailability of leptin in human plasma. ..
  80. Gonias S, Carmichael A, Mettenburg J, Roadcap D, Irvin W, Webb D. Identical or overlapping sequences in the primary structure of human alpha(2)-macroglobulin are responsible for the binding of nerve growth factor-beta, platelet-derived growth factor-BB, and transforming growth factor-beta. J Biol Chem. 2000;275:5826-31 pubmed
    ..Thus, FP3 may inhibit the activity of PDGF-BB. ..
  81. Garber T, Gonias S, Webb D. Interleukin-4 and IL-10 bind covalently to activated human alpha2-macroglobulin by a mechanism that requires Cys949. J Interferon Cytokine Res. 2000;20:125-31 pubmed
    ..In these complexes, Cys949 is properly aligned to undergo thiol disulfide exchange and generate stable, covalent IL-4-alpha2M and IL-10-alpha2M complexes. ..
  82. Schweer D, Jacobsen M, Ziegler A, Jäkel S, Oertel W, Sommer N, et al. No association of three polymorphisms in the alpha-2-macroglobulin and lipoprotein related receptor genes with multiple sclerosis. J Neuroimmunol. 2001;118:300-3 pubmed
    ..Furthermore, no differences in serum A2M levels were detected between MS patients and controls. The results do not suggest a contribution of A2M and LRP to the development of MS. ..
  83. Kolodziej S, Wagenknecht T, Strickland D, Stoops J. The three-dimensional structure of the human alpha 2-macroglobulin dimer reveals its structural organization in the tetrameric native and chymotrypsin alpha 2-macroglobulin complexes. J Biol Chem. 2002;277:28031-7 pubmed
    ..This extraordinary change in the architecture of alpha(2)M functions to completely engulf two molecules of chymotrypsin within its central cavity and to irreversibly encapsulate them. ..
  84. Lo H, Hsu S, Ali Seyed M, Gunduz M, Xia W, Wei Y, et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell. 2005;7:575-89 pubmed
    ..Our work suggests that the deregulated iNOS/NO pathway may partly contribute to the malignant biology of tumor cells with high levels of nuclear EGFR and STAT3. ..
  85. Doan N, Gettins P. Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3. Biochem J. 2007;407:23-30 pubmed
  86. Luan Y, Kong L, Howell D, Ilalov K, Fajardo M, Bai X, et al. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthritis Cartilage. 2008;16:1413-20 pubmed publisher
    ..Furthermore, a(2)M is a novel substrate for ADAMTS-7 and ADAMTS-12. More significantly, a(2)M represents the first endogenous inhibitor of ADAMTS-7 and ADAMTS-12. ..