Sequence and acute phase regulation of rat alpha 1-inhibitor III messenger RNA.

Braciak, Todd A.; Northemann, Wolfgang; Hudson, GS; Shiels, Brian; Gehring, Michael R.; Fey, Georg H.

doi:10.1016/s0021-9258(18)69025-8

Cited by 74 publications

(36 citation statements)

References 61 publications

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“…rat α 1 M [44], murinoglobulins 1 and 2 [45] and rat α 1 I 3 [46]) one side of the molecule has a strikingly conserved strip of residues from the tip to the bottom (Figure 3). The conserved strip can be divided into two patches, one located at the upper end of the molecule and the other on the lower middle part of the molecule.…”

Section: Proposed Receptor-recognition Sitementioning

confidence: 99%

Crystal structure of the receptor-binding domain of α2-macroglobulin

et al. 1998

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The surface patch responsible for receptor recognition is thought to involve residues located on one of the two alpha helices of the bRBD as well as residues in two of the beta strands. Located on this alpha helix are two lysine residues that are important for receptor binding. The structure of bRBD is very similar to the approximately 100-residue C-terminal domain of factor XIII, a transglutaminase from the blood coagulation system.

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Section: Proposed Receptor-recognition Sitementioning

confidence: 99%

Crystal structure of the receptor-binding domain of α2-macroglobulin

et al. 1998

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“…This situation is different from the rat aqU genes, which form a small gene family. Under similar experimental conditions as those used here, at least four different a, 13 genes were found in the rat genome (Braciak et al, 1988; Northemann et at., 1988b). It is not known whether an equivalent of the a, 13 gene family exists in the human genome, but from the sequence relatedness it is clear that rat a2M is the equivalent of human a2M.…”

Section: Discussionmentioning

confidence: 52%

“…Hayashida and colleagues (Hayashida et al, 1986) Alignment of the S'-terminal regions of the a2M and genes. The 5'-terminal regions of the a2M gene (Figure 4) and the prototype aiI13 gene (Braciak et al, 1988;Northemann et al, 1988b) were manually aligned. Gaps were introduced to achieve optimal alignment and are designated by dots.…”

Section: Discussionmentioning

confidence: 99%

“…Preparation of RNA, Size Enrichment, and Northern Blot Analysis. These experiments were performed as previously described (Gehring et al, 1987;Northemann et al, 1985;Braciak et al, 1988;Shiels et al, 1987). RNA from H35 hepatoma cells (Baumann et al, 1987) was prepared with guanidinium thiocyanate and sedimented through a cesium chloride cushion (Turpen & Griffith, 1986).…”

Section: Methodsmentioning

confidence: 99%

“…All a-macroglobulins are proteinase inhibitors of high molecular weight. All members of this family contain an internal thiolester bond, which is important for their function, and all are structurally related (Lonberg-Holm et al, 1987;Sottrup-Jensen, 1987; Gehring et al, 1987;Braciak et al, 1988; Gauthier & Ohlsson, 1978;Esnard & Gauthier, 1980;Schaeufele & Koo, 1982). The a-macroglobulins are further structurally related to complement components C3, C4, and C5, and the genes for all family members have evolved from a common ancestor (Sottrup-Jensen et al, 1985;Sottrup-Jensen, 1987).…”

mentioning

confidence: 99%

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Structure and acute-phase regulation of the rat .alpha.2-macroglobulin gene

Northemann¹,

Shiels²,

Braciak³

et al. 1988

Biochemistry

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Seven genomic DNA clones representing the rat alpha 2-macroglobulin gene were isolated and characterized. The cloned sequence covered the entire gene (48 kilobases) plus 2 kilobases of 3'- and 13.7 kilobases of 5'-flanking sequences. A restriction cleavage map of the gene was produced, and the restriction cleavage pattern of genomic DNA suggested that the alpha 2-macroglobulin gene is a single-copy gene. A 7.7-kilobase fragment from the 5'-terminal region and a 250 base pair fragment from the 3'-terminal region of the gene were sequenced, and the 3' end of the gene was mapped. The sequenced 5'-terminal fragment contained 4.5 kilobases of 5'-flanking sequences plus the first three exons and two introns of the gene. Two transcription start sites, a minor and a major site, located 65 nucleotides apart, were defined by primer extension, S1 mapping, and RNaseH experiments. During an acute-phase response, transcription from both sites was induced in the liver, and over 90% of the transcripts originated from the major site. Very high concentrations of alpha 2-macroglobulin mRNA originating from both start sites were also found in the uterus but not in the liver of pregnant females. A glucocorticoid response element (GRE), a conserved consensus sequence for a potential glucocorticoid receptor DNA binding site, was found by computer search in the promoter-proximal 5'-flanking region of the alpha 2-macroglobulin gene.

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Binding of rat α1-inhibitor-3-methylamine to the α2-macroglobulin signaling receptor induces second messengers

1996

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Binding of receptor-recognized forms of tetrameric human alpha 2-macroglobulin (alpha 2M*) to a macrophage signaling receptor induces cAMP synthesis, increases in inositol 1,4,5-triphosphate (IP3) synthesis, and a concomitant rise in cytosolic free calcium ([Ca2+]i). The alpha 2M* signaling receptor is coupled to a pertussis-toxin insensitive G protein. Binding of alpha 2M* also occurs to the low density lipoprotein receptor-related protein/alpha 2M receptor (LRP/alpha 2MR), but this binding does not induce signal transduction. Rat alpha 1-inhibitor-3 (alpha 1I3) is a monomeric member of the alpha-macroglobulin/complement superfamily. Like alpha 2M, it can react with proteinases or methylamine which induces a conformational change causing activated alpha 1I3 to bind to LRP/alpha 2MR. We now report that alpha 1I3-methylamine binds to the macrophage alpha 2M* signaling receptor inducing a rapid rise in the synthesis of IP3 with a subsequent 1.5- to 3-fold rise in [Ca2+]i. alpha 1I3-methylamine binding to macrophages also caused a statistically significant elevation in cAMP. Native alpha 1I3, like alpha 2M, was unable to induce signal transduction. alpha 1I3 forms a complex with alpha 1-microglobulin, which has a distinct conformation from alpha 1I3 and is recognized by LRP/alpha 2MR. This complex also induces an increase in [Ca2+]i comparable to the effect of alpha 1I3-methylamine on macrophages. It is concluded that activation of alpha 1I3 by methylamine or binding of alpha 1-microglobulin causes similar conformational changes in the inhibitor, exposing the receptor recognition site for the alpha 2M* signaling receptor, as well as for LRP/alpha 2MR.

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Sequence and acute phase regulation of rat alpha 1-inhibitor III messenger RNA.

Cited by 74 publications

References 61 publications

Crystal structure of the receptor-binding domain of α2-macroglobulin

Crystal structure of the receptor-binding domain of α2-macroglobulin

Structure and acute-phase regulation of the rat .alpha.2-macroglobulin gene

Binding of rat α1-inhibitor-3-methylamine to the α2-macroglobulin signaling receptor induces second messengers

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