Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium, acting as second messenger, are through-target proteins that contain an EF-hand structure. Based on this general principle, EF-hand structures can be predicted from the amino acid sequence of a protein. Most recently, several new members of the Ca2+-binding protein family have been discovered, e.g., the cystic fibrosis antigen (CFAg), the macrophage migration inhibitory factor related proteins (MRP-8 and -14), non-muscle alpha-actinin, and uvomorulin, the latter belonging to the group of cell adhesion molecules. Additionally, new information about the physiological functions of S-100 proteins, calbindins, calretinin as well as parvalbumin were observed and some of the these results are discussed.
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PMID:Calcium-binding proteins of the EF-type. 246 75

Oncomodulin (ONCO) is an oncodevelopmental protein expressed in placental and extraembryonic tissue and re-expressed in a wide variety of tumors. The metallothionein promoter (MT) is active in numerous adult tissues, in parietal and visceral extraembryonic endoderm, and developing liver. To study the function of oncomodulin we microinjected MT-ONCO DNA into one-cell embryos and examined tissues of fetal and adult mice. Analysis of implant sites from embryos, microinjected with MT-ONCO DNA then placed into pseudopregnant females, indicated a greater than three-fold increase in empty and necrotic implant sites relative to SV2NEO-microinjected embryos and a seven-fold rise relative to non-microinjected embryos. The striking feature of the lethality was the presence of a normal placenta but absence of fetal tissue. Few MT-ONCO DNA transgenic mice were isolated (3.5%) and none were able to express oncomodulin protein or RNA in any tissue examined, even after prolonged heavy metal stimulation of the MT promoter. Fetal mortality is best correlated with expression of oncomodulin causing an interruption of either cellular differentiation or organogenesis before day 9 in development.
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PMID:Microinjection of metallothionein-oncomodulin DNA into fertilized mouse embryos is correlated with fetal lethality. 247 84

We have used monoclonal antibodies to study the expression of calgranulins by keratinocytes in inflammatory dermatoses. Calgranulins are intracellular calcium binding proteins which have inflammatory cytokine activity and are composed of at least two different chains, calgranulin A and B. Antibody CF 145 and CF 557 identify calgranulin A and B, respectively. MAC 387 recognizes a molecule probably containing both calgranulins. Keratinocytes in normal skin did not contain these molecules. The keratinocytes in 52 cases of different inflammatory dermatoses showed expression of both calgranulin chains in lesional but not in non-lesional skin. Keratinocytes in inflammatory dermatoses therefore express an intracellular calcium binding protein which has cytokine activity.
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PMID:Calgranulin expression in inflammatory dermatoses. 247 83

Two associated calcium-binding proteins (CaBPs) have recently been identified specifically in cells of myeloid origin. These proteins have relative molecular masses (Mr) of 8,000 and 14,000 and are variously referred to as the cystic fibrosis antigen, the L1 light chain, MRP-8 or p8, and the L1 heavy chain, MRP14 or p14, respectively. The expression of p8 and p14 seems to be confined to a specific stage of myeloid cell differentiation, because both proteins are expressed in circulating neutrophils and monocytes but not in normal tissue macrophages. In chronic inflammatory conditions, however, such as rheumatoid arthritis, macrophages in affected tissues express both p8 and p14. These proteins are members of a family of CaBPs of low Mr, which include S-100 alpha and beta proteins, calcyclin (2A9), intestinal CaBP and p11. All the proteins have an Mr of approximately 10,000 with the exception of p14 which has a longer C-terminal sequence after the second calcium-binding domain. Little is known about their function, although by analogy with calmodulin they could be molecules involved in intracellular signalling that are activated by an increase in the intracellular Ca2+ concentration ([Ca2+]). Here we report that p14 is phosphorylated in both monocytes and neutrophils. The level of p14 phosphorylation can be increased by elevating the [Ca2+]i using the ionophore ionomycin, but is not affected by activation of protein kinase C using phorbol 12,13-dibutyrate. The phosphorylated residue is threonine at position 113, which is the penultimate amino acid in p14 and contained in the longer 'tail' sequence. Part of this sequence is identical to the neutrophil immobilizing factors NIF-1 and NIF-2, indicating that the phosphorylation event could have a role in the generation of NIF activity in the p14 protein.
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PMID:Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14. 247 89

The histone H4 multigene family of Physarum polycephalum consists of two genes, H41 and H42. Both genes have an unusual structure in that they are interrupted by a small intron. The structure of the P. polycephalum H4 genes is discussed and compared to the structure of histone genes of other organisms. S1 nuclease analysis was used to map the 5' and 3' ends of the histone H4 messengers. We show that the histone H4 genes have a hybrid structure; they are interrupted by an intervening sequence, as in replacement variant histone genes of higher eukaryotes, but their 5' and 3' noncoding regions have the properties of replication-dependent histone genes: the 5' and 3' leader and trailer sequences are short, possess a 3'-hyphenated dyad symmetry element, and a CAGA sequence is found 3' to the hyphenated hairpin structure. This report also provides evidence that both genes are expressed in late G2 phase as well as in S phase and that their expression is temporally coordinated and quantitatively similar during the cell cycle.
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PMID:Histone genes in Physarum polycephalum: transcription and analysis of the flanking regions of the two H4 genes. 249 87

We have cloned and sequenced a meiotic recombinational hotspot between the A beta 3 and A beta 2 genes in the major histocompatibility complex (MHC) of the mouse. This recombinational hotspot in the Mus musculus castaneus cas3 haplotype was previously localized to a region of 9.5 kb of DNA in which five independent crossing-over events occurred at the unusually high frequency of 0.6%. Aside from cas3, the hotspot appears to be absent in many other MHC haplotypes. We have now confined the five recombinational breakpoints to a stretch of 3.5 kb of DNA. From the nucleotide sequence around the recombinational breakpoints, determined in the parental cas3 and b haplotypes as well as for two recombinant haplotypes, we show that the two recombinant haplotypes were generated by homologous equal crossing-over and place the breakpoints within two non-overlapping stretches of 10 and 36 bp, respectively. Comparison of the DNA sequences of the hotspot-positive cas3 and the hotspot-negative b haplotypes reveals a number of differences, in particular, a CAGA-repeat sequence which is present in CAS3 in six, but only four copies in C57BL/6 DNA. This repeat sequence is reminiscent of one in a previously characterized hotspot in the E beta gene.
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PMID:Molecular characterization of a meiotic recombinational hotspot enhancing homologous equal crossing-over. 302 57

We cloned and characterized the gene encoding H1-gamma, a late histone subtype of the sea urchin species Strongylocentrotus purpuratus. The predicted primary sequence of H1-gamma is 216 amino acids in length and has a net charge of +70, which is high for a somatic H1 histone. The H1-gamma gene appears to be a unique sequence gene that is not tightly linked to the core histone genes. The 770-base-pair transcribed region of the H1-gamma gene is bordered on the 5' side by two previously described H1-specific sequence elements and on the 3' side by a hairpin loop structure and CAGA box sequences. We detected 3,900 stored maternal H1-gamma mRNA transcripts per egg. The number of H1-gamma transcripts per embryo rises by 9.5 h postfertilization, but the maximum rate of accumulation (4,300 molecules per min per embryo) occurs in the late-blastula-stage embryo between 14 and 21 h after fertilization. The number of H1-gamma mRNA molecules peaks 21 h after fertilization when there are 2.0 X 10(6) molecules per embryo (a 500-fold increase) and then decreases over the next 3.25 h to 1.3 million molecules per embryo. Between 24 and 82 h after fertilization the number of H1-gamma transcripts declines steadily (210 molecules per min per embryo) to reach approximately 5.4 X 10(5) H1-gamma mRNAs by 82 h postfertilization. Surprisingly, the number of late H1 mRNA molecules per embryo is greater than the number of late H2B mRNA molecules beginning at the early gastrula stage of development.
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PMID:Isolation, characterization, and expression of the gene encoding the late histone subtype H1-gamma of the sea urchin Strongylocentrotus purpuratus. 303 76

Using a monoclonal antibody to macrophage migration inhibition factor (MIF), two proteins were isolated from supernatants of Concanavalin A-stimulated human peripheral blood mononuclear cells which seem to have complexed to a third component carrying the MIF activity. They are therefore designated MIF-related proteins or MRP-8 and MRP-14 according to their apparent molecular weights. Partial amino acid sequences have been determined and their cDNA have been cloned and expressed in Escherichia coli. Both are calcium-binding proteins and MRP-8 seems to be largely homologous to the cystic fibrosis antigen (Dorin et al., 1987). Antisera were raised in the rabbit against the recombinant proteins and their expression in cells and tissues studied using immunohistological techniques. The proteins are only found in blood granulocytes and monocytes. In culture the number of positive monocytes sharply increased and then declined with time, suggesting that their expression is associated with early stages of monocyte/macrophage differentiation and absent from resident macrophages in all tested tissues. In acute inflammatory reactions, e.g. gingivitis, MRP-8 is never seen in the tissue, whereas MRP-14 is expressed by intravascular monocytes and perivascular macrophages. In contrast, in chronic inflammation, e.g. rheumatoid arthritis, MRP-8 is also expressed by macrophages in the tissue. From this it is concluded that MRP-8 and MRP-14 are expressed sequentially at defined stages of monocyte/macrophage differentiation and that dysregulation of this process in chronic inflammation is mirrored by the presence of MRP-8-positive macrophages in the tissue.
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PMID:Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. 304 9

This paper reports further study of the identity and function of a protein shown to be elevated in serum from cystic fibrosis (CF) patients and clinically normal heterozygotes. Monoclonal antibodies, specifically recognizing the tentatively named cystic fibrosis antigen (CFAg), were produced. Immunoaffinity purification of CFAg from several sources revealed two components: 11 x 10(3) and 14 x 10(3) Mr protein. cDNA clones corresponding to each protein have been isolated. Data-base comparisons of the deduced amino acid sequences suggest that both genes encode related but distinct calcium-binding proteins. We propose the name calgranulin A and B, for the 11 x 10(3) and 14 x 10(3) Mr components, respectively. It is clear from the assignment of the calgranulin genes to chromosome 1 that neither is the product of the mutant CF gene, which maps to chromosome 7. We have used the monoclonal antibodies to study the tissue distribution of the two proteins in a wide-ranging immunohistological survey. Where possible the pattern of expression was confirmed by RNA blot analysis. Strong calgranulin expression in granulocytes was confirmed. In addition to myeloid cells, a restricted subset of normal stratified squamous epithelia were found to be calgranulin-positive. These included tongue, oesophagus and buccal cells, the last of which has been shown to have altered calmodulin activity in CF patients. Using indirect alkaline phosphatase staining, tissue sections of lung, pancreas and skin (normally considered sites where the CF defect is expressed) were not calgranulin-positive. However, by indirect immunofluorescence, nasal polyp sections showed weak patchy calgranulin expression in some epithelial cells, and stronger, higher frequency expression when such cells were briefly cultured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression pattern of two related cystic fibrosis-associated calcium-binding proteins in normal and abnormal tissues. 326 95

The aetiology and cellular mechanism of chronic inflammatory processes are poorly understood. Macrophages act prominently in the inflammatory response and we report here that they express two calcium-binding proteins. The expression of these proteins, referred to as MRP-8 and MRP-14, is specific for cells of myeloid origin, namely granulocytes, monocytes and macrophages, and is observed in blood granulocytes and monocytes but not in normal tissue macrophages. In acutely inflamed tissues, macrophages can express MRP-14 but not MRP-8, and in chronic inflammations, such as primary chronic polyarthritis, infiltrate macrophages express both MRP-8 and MRP-14. Characterization of MRP-8 and MRP-14 could therefore be useful to the understanding of cellular processes induced in chronic inflammation.
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PMID:Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. 331 57


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