The α macroglobulins of rat serum

Gordon, A. H.

doi:10.1042/bj1590643

Cited by 107 publications

(51 citation statements)

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“…The possibility exists that more than one a2M locus or cross-hybridizing loci might be present on chromosome 12, in analogy to the duplicated C4 loci on chromosome 6. Rats and rabbits have two a-macroglobulins in their serum: a1-macroglobulin (a1M) and a2M (4). Both are similar in size, are proteinase inhibitors, contain thiol ester bonds, share antigenic determinants, and show similar amino acid composition and glycosylation patterns (4).…”

Section: E a S P A F L A V P V E K E A P H C I C A N G R 0 T V S W mentioning

confidence: 99%

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Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Kan¹,

Solomon²,

Belt³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Six a2-macroglobulin (a2M) cDNA clones were isolated from a human liver cDNA library by using synthetic oligonucleotides as hybridization probes. One of these, pa2M1, carries a 4.6-kilobase-pair insert, which was sequenced. The insert contains the coding sequences for the mature a2M polypeptide (1451 amino acids) and for a 23-amino acid signal peptide at the NH2 terminus of the precursor proa2M. At the 3' end of the insert a poly(A) addition signal A-A-T-A-A-A and part of the poly(A) tail of the messenger RNA were found. The protein sequence deduced from the nucleotide sequence agrees with the published a2M amino acid sequence for all except three residues. The a2M locus was assigned to human chromosome 12 by Southern blot analysis with DNA from a panel of mouse/human somatic cell hybrids, using a2M cDNA as a hybridization probe.a2-Macroglobulin (a2M) is a serum glycoprotein and a major plasma proteinase inhibitor with a wide specificity. a2M-related proteins are present in all vertebrate species (1-4). Human a2M is a tetramer of four identical 185-kDa subunits, arranged as a pair of dimers each consisting of two disulfidelinked monomers (5, 6). The a2M polypeptide has a so-called bait region and an internal thiol ester bond, which account for its properties as a proteinase inhibitor. The bait region, composed of a series of target peptide bonds for plasma proteinases (7, 8) (13,14).This suggests that the conformational change, which accompanies the complex formation between a2M and proteinases and the hydrolysis of the thiol ester bond, exposes regions of the a2M molecule that are recognized by these receptors. Receptor-mediated endocytosis of proteinase-a2M complexes by macrophages and liver cells leads to clearance of the complexes from the circulation.Internal thiol ester bonds are also found in the complement proteins C3 and C4 (15), which are derived from precursor polypeptides of size similar to a2M (180-200 kDa). Their thiol ester sites are found in positions comparable to those in a2M, and the amino acid sequences of all three thiol ester sites are conserved. These observations led to the proposal that the C3, C4, and a2M genes are derived from a common ancestral gene (16). The sequences of murine and human C3 and human C4 and partial cDNA sequences of murine C4 have recently been determined (17-21). Comparison of human a2M with murine C3 revealed a 25% overall sequence homology (17,18,22

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Section: E a S P A F L A V P V E K E A P H C I C A N G R 0 T V S W mentioning

confidence: 99%

“…a2M-related proteins are present in all vertebrate species (1)(2)(3)(4). Human a2M is a tetramer of four identical 185-kDa subunits, arranged as a pair of dimers each consisting of two disulfidelinked monomers (5,6).…”

mentioning

confidence: 99%

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Kan¹,

Solomon²,

Belt³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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“…a2-Macroglobulin inhibits the majority of proteinases regardless of their catalytic mechanisms [lo-131. In the serum of normal rats a2-macroglobulin is present in extremely low concentrations and increases during inflammation about 1 00-fold [3,5,7]. There is not much known about the mechanism(s) responsible for this increase.…”

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confidence: 99%

“…In the rat the best indicators of acute inflammation are a2-macroglobulin, al-acid glycoprotein, and al-acute phase globulin [3 -81. Their plasma levels show dramatic increases in comparison to those of healthy animals.Rat a2-macroglobulin is a plasma proteinase inhibitor of a molecular weight of about 700000, it is composed of four probably identical subunits [3,5,9]. a2-Macroglobulin inhibits the majority of proteinases regardless of their catalytic mechanisms [lo-131.…”

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Cell‐free synthesis of rat α₂‐macroglobulin and induction of its mRNA during experimental inflammation

Northemann

Andus

Groß

et al. 1983

European Journal of Biochemistry

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Poly(A)-rich RNA was isolated from the livers of acutely inflamed rats by extraction with guanidinium HCl and oligo(dT)-cellulose chromatography. After translation in a recticulocyte lysate and immunoprecipitation with a specific antiserum to a2-macroglobulin a polypeptide with an apparent molecular weight of 162000 could be detected. The cell-free synthesis of a2-macroglobulin was stimulated 8-fold by the addition of RNasc inhibitor. Fulllength a2-macroglobulin polypeptide chains appeared after 35 min in the presence of 1.85 mM Mg2+ and 100 mM K + . A nucleotide number of about 5100 was estimated for a2-macroglobulin by means of sucrose gradient centrifugation of poly(A)-rich RNA followed by translation in uitro and immunoprecipitation of a2-macroglobulin.In normal liver a2-macroglobulin mRNA represented about 0.0007 % of total translatable RNA. Acute inflammation generated by intramuscular injection of turpentine led to a 66-fold increase in translatable a2-macroglobulin mRNA after 18 h, followed by a rapid decrease. In accordance to the induction of 1x2-macroglobulin mRNA serum concentrations of 1x2-macroglobulin increased to about 2 mg/ml. Unlike a2-macroglobulin mRNA serum a2-macroglobulin levels remained unchanged up to 60 h. Local inflammation, thermal or mechanical injury, major surgery, bacterial infection or endotoxin injection and neoplasmic growth lead to increased concentrations of acutephase proteins (reviewed in [1,2]). Thus far, all acute-phase proteins have been found to be glycoproteins synthesized in the liver and secreted into the blood. In the rat the best indicators of acute inflammation are a2-macroglobulin, al-acid glycoprotein, and al-acute phase globulin [3 -81. Their plasma levels show dramatic increases in comparison to those of healthy animals.Rat a2-macroglobulin is a plasma proteinase inhibitor of a molecular weight of about 700000, it is composed of four probably identical subunits [3,5,9]. a2-Macroglobulin inhibits the majority of proteinases regardless of their catalytic mechanisms [lo-131. In the serum of normal rats a2-macroglobulin is present in extremely low concentrations and increases during inflammation about 1 00-fold [3,5,7]. There is not much known about the mechanism(s) responsible for this increase. As a first approach to this problem we have studied the a2-macroglobulin mRNA synthesis in rat liver. Up to now experiments on the induction of mRNA for al-acid glycoprotein [6], fibrinogen [14], al-proteinase inhibitor [15,16], serum amyloid A [17], and haptoglobin [18] have been published. In the present paper we describe first the cell-free synthesis of rat a2-macroglobulin (a preliminary report has already been published [19]) and then measurements of translatable a2-macroglobulin mRNA levels at different times after intramuscular turpentine injections and their comparison to the a2-macroglobulin concentrations in rat serum. MATERIALS AND METHODS Chemicals AnimalsMale Wistar rats of 250 g body weight were generously supplied by Prof. Dr H. Ueberbcrg, Thomae GmbH, Bib...

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Partial purification and characterization of serum embryotrophic factor required for early postimplantation growth of rat embryos in culture

Usami

Ohno

1996

J. Exp. Zool.

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Serum embryotrophic factor (SEF) required for the growth of cultured post‐implantation rat embryos was partially purified from rat serum. Rabbit serum was used as a basal medium for the embryo culture, and embryotrophic activity was measured as embryonic protein increase. For partial purification of SEF, the rat serum globulin fraction obtained by ultra‐centrifugation and (NH4)2SO4 precipitation was fractionated by gel filtration, diethylaminoethyl ion‐exchange chromatography, and hydroxyapatite chromatography. Partially purified SEF was characterized by stability tests and affinity chromatography. SEF was inactivated by heat, acid, dithiothreitol reduction, or trypsin digestion. SEF bound to concanavalin A but not to heparin. These results indicated that SEF was an acid‐labile acidic glycoprotein with disulphide bonds and no affinity for heparin. The Mr of SEF was estimated to be about 180 × 103 by gel filtration. The specific activity (U/g protein) was increased about 25‐fold with 9.4% recovery by the partial purification, when 1 U of SEF was defined as the amount giving 50% embryonic protein increase. By polyacrylamide gel electrophoresis, a protein most likely to be SEF was identified as a heterodimer composed of subunits of Mr‐ 116 × 103 and 62 × 103 linked by disulphide bonds, and was shown to be contained in the medium at micromolar concentrations. SEF appeared to be distinct from known protein embryotrophic factors, growth factors, or cytokines. © 1996 Wiley‐Liss, Inc.

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The α macroglobulins of rat serum

Cited by 107 publications

References 31 publications

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Cell‐free synthesis of rat α₂‐macroglobulin and induction of its mRNA during experimental inflammation

Partial purification and characterization of serum embryotrophic factor required for early postimplantation growth of rat embryos in culture

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The α macroglobulins of rat serum

Cited by 107 publications

References 31 publications

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Cell‐free synthesis of rat α2‐macroglobulin and induction of its mRNA during experimental inflammation

Partial purification and characterization of serum embryotrophic factor required for early postimplantation growth of rat embryos in culture

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Cell‐free synthesis of rat α₂‐macroglobulin and induction of its mRNA during experimental inflammation