Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera from patients with connective tissue diseases often contain antibodies against snRNA-associated proteins. Using one of these sera in an immunological screening of a human lambda gt11 expression vector cDNA library, two cDNA clones for the U1 snRNP-specific A protein, termed lambda HA-1 and lambda HA-2, were isolated. Monospecific antibodies, eluted from the beta-galactosidase fusion protein of either clone reacted with the U1 snRNP-specific A antigen. The identity of the clones was confirmed by in vitro translation of hybrid selected mRNA. RNA blot analysis revealed a single polyadenylated transcript of about 1.4 kb in human cells. A cDNA of 1.2 kb, isolated from the same lambda gt11 expression library by cross-hybridization with a lambda HA-2 restriction fragment, covered the complete coding sequence of the A protein as demonstrated by in vitro translation of an RNA transcript synthesized from this cDNA. The deduced amino acid sequence contains one very hydrophilic region, and internal sequence duplication and a region highly homologous to the RNP consensus sequence that seems to be common to RNA binding proteins. Sequence comparison with the recently cloned U2 snRNP-specific B" protein revealed two extremely homologous regions located in the carboxy-terminal (homology of 86%) and amino-terminal part (homology of 77%) of the proteins. This structural relationship indicates that proteins A and B", although located in different snRNP particles, may have identical functions.
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PMID:cDNA cloning of the human U1 snRNA-associated A protein: extensive homology between U1 and U2 snRNP-specific proteins. 296 59

Following heat shock the expression of heat shock genes is regulated by the heat shock transcription factor, HSF, known to bind to arrays of the heat shock element, NGAAN, upstream of the heat shock genes. Phosphorylation of HSF is necessary for its activation. We report that the treatment of Chinese hamster HA-1 cells with 250 nM of okadaic acid (OA), a ser/thr phosphatase inhibitor, leads to an increase in activated HSF after heat shock. This is followed by the activation of the transcription of heat shock genes as assayed by the increase in the synthesis of beta-galactosidase in an HA-1 cell line containing the heat shock promoter ligated to the beta-galactosidase gene. To investigate the specificity of OA, we used other phosphatase inhibitors. We found that treatment of HA-1 cells with 500 microM of sodium vanadate, an inhibitor of tyr/phosphatases, resulted in a three to fivefold reduction in HSF activation and binding to the heat shock element following heat shock. Such reduction in HSF activation virtually abolished beta-galactosidase induction. Reduced HSP synthesis was further confirmed by SDS-PAGE and Western blot analysis using anti-HSP-70 and 28 antibodies. Sodium vanadate treatment of heat shocked cells greatly reduced levels of thermotolerance. These results show that ser/thr and specifically tyr/phosphatase inhibitors modulate the signal transduction pathway of HSF activation.
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PMID:Inhibitors of tyrosine and Ser/Thr phosphatases modulate the heat shock response. 817 93

Major histocompatibility complex (MHC) class I molecules present peptides from endogenous proteins. However, in some cases class I-restricted peptides can also derive from exogenous antigens. This MHC class I exogenous presentation could be involved in minor histocompatibility antigen (mHAg)-disparate allograft rejection when donor alloantigens are not expressed in graft antigen-presenting cells (APC) that initiate the rejection mechanism. Here we addressed this question by using a skin graft experimental model where donors (H-2b or H-2d Tg beta-gal mice) expressed the mHAg like beta-galactosidase (beta-gal) in keratinocytes but not in Langerhans' cells (LC) which have an APC function. Rejection of Tg beta-gal skin by a beta-gal-specific CD8 cytotoxic T lymphocyte (CTL) effector mechanism should require presentation by donor and/or recipient LC of MHC class I-restricted peptides of exogenous beta-gal shed by keratinocytes. Indeed, our results showed that 1) H-2b Tg beta-gal skin was rejected by H-2bxs and H-2bxd recipients; 2) rejection was mediated by beta-gal-specific CD8+ CTL effectors; and 3) H-2bxd mice having rejected H-2b Tg beta-gal skin generated beta-gal-specific CTL restricted by H-2b and H-2d class I molecules and rejected subsequently grafted H-2d Tg beta-gal skin in an accelerated fashion, demonstrating that recipient LC have presented exogenous beta-gal-derived MHC class I epitopes. These results lead to the conclusion that MHC class I exogenous presentation of donor mHAg can initiate allograft rejection.
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PMID:Major histocompatibility complex class I presentation of exogenously acquired minor alloantigens initiates skin allograft rejection. 946 40

Endothelial cells (ECs) presenting minor histocompatibility antigen (mhAg) are major target cells for alloreactive effector CD8(+) T cells during chronic transplant rejection and graft-versus-host disease (GVHD). The contribution of ECs to T-cell activation, however, is still a controversial issue. In this study, we have assessed the antigen-presenting capacity of ECs in vivo using a transgenic mouse model with beta-galactosidase (beta-gal) expression confined to the vascular endothelium (Tie2-LacZ mice). In a GVHD-like setting with adoptive transfer of beta-gal-specific T-cell receptor-transgenic T cells, beta-gal expression by ECs was not sufficient to either activate or tolerize CD8(+) T cells. Likewise, transplantation of fully vascularized heart or liver grafts from Tie2-LacZ mice into nontransgenic recipients did not suffice to activate beta-gal-specific CD8(+) T cells, indicating that CD8(+) T-cell responses against mhAg cannot be initiated by ECs. Moreover, we could show that spontaneous activation of beta-gal-specific CD8(+) T cells in Tie2-LacZ mice was exclusively dependent on CD11c(+) dendritic cells (DCs), demonstrating that mhAgs presented by ECs remain immunologically ignored unless presentation by DCs is granted.
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PMID:Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen. 1844 Dec 41