Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene encoding steroid 21-hydroxylase activity, P450c21B, is located in the major histocompatibility complex (MHC) class III region, in close proximity to a highly homologous pseudogene, P450c21A. Recombinations between P450c21B and P450c21A have been shown to result in deficiency of 21-hydroxylase activity, the usual cause of congenital adrenal hyperplasia (CAH). A mutant P450c21 gene from a patient with simple virilizing CAH was identified and shown to be consistent with a recombination between P450c21A and P450c21B. Sequence analysis of the mutant gene showed the recombination site to be located between the first exon and the second intron. The mutant gene encodes a leucine instead of the normal proline at codon 31. This mutation resides on a chromosome bearing the HLA-B44 serotype. A comparison of mutations associated with HLA-B44 and that normally found with the HLA-Bw47 serotype suggests that the HLA-B44 mutations are of more ancient origin. The patient's homologous chromosome has a deletion of P450c21B. Endocrinological testing therefore allows for testing of the mutant gene in genetic isolation. Such testing demonstrated that the patient was capable of producing aldosterone and retaining sodium in response to a low-sodium diet, indicating that the mutant gene encodes an enzyme with partial 21-hydroxylase activity.
J Steroid Biochem Mol Biol 1991 Jun
PMID:Molecular and endocrine characterization of a mutation involving a recombination between the steroid 21-hydroxylase functional gene and pseudogene. 190 48

In earlier studies, we had determined that class II (Ia) major histocompatibility complex (MHC) antigen expression in the normal rat lung was limited to dendritic cells and type II alveolar cells. In order to characterize the Ia+ pulmonary dendritic cells of the lung parenchyma, Lewis rat lungs were dissected free of their major airways, enzymatically digested, and serially subjected to density centrifugation on bovine serum albumin, overnight adherence, and immunopanning with a murine anti-rat monoclonal antibody (anti-OX-6) that reacts specifically with class II (Ia) MHC antigens. The purified Ia+ pulmonary cells displayed the morphologic and functional features of dendritic accessory cells, including extended cell processes, absence of nonspecific esterase staining, minimal phagocytosis of latex beads, rapid clustering with T lymphocytes, and co-stimulation of T-cell mitogen responses. Detailed immunophenotyping by cytofluorimetry and immunohistology showed that the purified dendritic cells were Ia (OX-6)+, CD45R (OX-1)+, CD45Rb (OX-22)-, ICAM-1+, and OX-43-. As many as 50% of the cells bound heat-aggregated IgG, while a smaller percentage expressed the CD43 sialophorin antigens (W3/13) expressed by a variety of blood-derived cells, and/or the OX-41 and RMA macrophage antigens. We conclude that Ia+ dendritic cells of lung are heterogeneous with respect to their expression of surface membrane differentiation antigens and may prove to be functionally distinct with respect to their accessory activities.
Am J Respir Cell Mol Biol 1991 Sep
PMID:Accessory cells of the lung. II. Ia+ pulmonary dendritic cells display cell surface antigen heterogeneity. 191 Aug 13

A DNA-binding factor with properties of NF-kappa B and another similar activity are rapidly induced when growth-arrested BALB/c 3T3 cells are stimulated with serum growth factors. Induction of these DNA-binding activities is not inhibited by pretreatment of quiescent cells with the protein synthesis inhibitor cycloheximide. Interestingly, the major NF-kappa B-like activity is not detected in nuclear extracts of proliferating cells, and thus its expression appears to be limited to the G0-to-G1 transition in 3T3 cells. These DNA-binding activities bind many of the expected NF-kappa B target sequences, including elements in the class I major histocompatibility complex and human immunodeficiency virus enhancers, as well as a recently identified NF-kappa B binding site upstream of the c-myc gene. Furthermore, both the class I major histocompatibility complex and c-myc NF-kappa B binding sites confer inducibility on a minimal promoter in 3T3 cells stimulated with serum growth factors. The results demonstrate that NF-kappa B-like activities are immediate-early response proteins in 3T3 cells and suggest a role for these factors in the G0-to-G1 transition.
Mol Cell Biol 1991 Oct
PMID:Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts. 192 27

Treatment of splenic B lymphocytes and certain B-lineage cell lines with the mitogen lipopolysaccharide (LPS) and the lymphokine interleukin-4 (IL-4) induces expression of germ line immunoglobulin C epsilon transcripts and class switching to the C epsilon gene. We show that LPS-plus-IL-4 induction of germ line epsilon transcripts (termed I epsilon transcripts) occurs at the transcriptional level in an Abelson murine leukemia virus-transformed pre-B-cell line. A 1.1-kb region of DNA surrounding the I epsilon promoter endows inducible transcription to a heterologous reporter gene stably transfected into these cells; such inducible expression depends on combined treatment with LPS and IL-4. Analyses of constructs transiently introduced into a B-cell lymphoma line demonstrated that LPS-plus-IL-4-inducible expression can be conferred by a 179-bp segment of DNA spanning the I epsilon transcriptional initiation site. Mutational analyses demonstrated that this expression depended on DNA sequences within a conserved region directly upstream from the I epsilon transcriptional initiation region. One nuclear protein that is constitutively expressed in normal B cells binds to the downstream end of the conserved sequence; its binding specificity correlates with the functional effect of several mutations. Two additional proteins, which are induced by IL-4 treatment of splenic B cells, bind to the transcription initiation sites of I epsilon. These proteins are indistinguishable in binding assays from proteins previously shown to bind an enhancer region of the class II major histocompatibility complex gene A alpha.
Mol Cell Biol 1991 Nov
PMID:Identification of a conserved lipopolysaccharide-plus-interleukin-4-responsive element located at the promoter of germ line epsilon transcripts. 192 63

Luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) receptors are coupled to intracellular effector systems, most notably adenylate cyclase, through guanyl nucleotide-binding proteins or G-proteins. The molecular mechanism involved in the dynamic coupling of the LH/hCG receptor however, are not known. It has been postulated that receptor aggregation at the molecular level plays a critical role in this process. There have been attempts to understand the receptor association and dissociation phenomena at the molecular level. One of them involves the participation of the major histocompatibility complex (MHC) class I antigen in the mechanism of receptor activation and/or expression. One molecular basis for these mechanisms consists of a physical interaction between MHC proteins and receptors to form "compound receptors" able to transfer a hormonal signal to the cell. Using a photo-reactive probe we demonstrated that the LH/hCG receptors and the class I antigens are closely associated in the membrane. Thus, it is possible to form covalent complexes of hCG and class I antigens through the binding of the hormone to specific receptors. These findings imply that LH/hCG receptors and the MHC class I antigens may interact at the level of the plasma membrane in the mechanism of LH action. We also performed experiments using a single cell and limiting stimulation to a patch of membrane. The results stimulating the cell in a localized area suggested that even if all components are entirely free to float there is a constraint in the localization of the receptor, G-protein, and/or the effector, supporting the constraint dissociation model. Within a limited area subunits could dissociate, but they would not be free to diffuse throughout the membrane. Moreover the concept of compartmentalization that has been utilized to explain some inconsistencies in second-messenger action now can be proved by experimental design.
J Steroid Biochem Mol Biol 1991
PMID:The action of luteinizing hormone on the testis. 195 45

We have investigated the expression of intercellular adhesion molecule-1 (ICAM-1) by novel functional human thyroid cell lines (designated SGHTL). ICAM-1 is constitutively expressed and it is rapidly upregulated in response to each of the recombinant cytokines: gamma-interferon, interleukin-1 and tumour necrosis factor. This contrasts with the more slowly increased expression of major histocompatibility complex (MHC) class II antigens in response to gamma-interferon alone. We have also demonstrated binding of activated lymphocytes to SGHTL cells: this interaction is increased following treatment with these cytokines and is inhibited by monoclonal antibodies directed against ICAM-1 or lymphocyte function-associated antigen-1 (LFA-1) but not by antibodies against CD2 or MHC class II antigens. Hence, we conclude that the binding of lymphoblasts to human thyroid cells involves an LFA-1- and ICAM-1-dependent pathway as well as other basal and cytokine-inducible pathway(s). These do not appear to involve MHC class II antigens, CD2 or an LFA-1 ligand other than ICAM-1.
Mol Cell Endocrinol 1990 May 28
PMID:Expression of intercellular adhesion molecule-1 (ICAM-1) on human thyroid cells lines correlated with their binding of lymphoblasts. 197 27

Most pleomorphic adenomas were found to contain abundant dendritic cells (DC) with major histocompatibility complex (MHC) class II (HLA-DR) expression. Their immunohistochemical staining features were suggestive of dendritic histiocytic cells. Extensive phenotypic characterization by two-colour immunofluorescence staining for various cell markers was performed. The DC expressed both HLA class I and II determinants, vimentin, S-100 protein, and various monocyte-related markers (10G11, 3D10, 7G5 or CD11a, 8C2) but were negative for leucocyte common antigen (CD45), Leu-6 (CD1), and the myelomonocytic L1 antigen. Characterization of HLA-DR positive DC isolated by an immunomagnetic bead method confirmed the immunohistochemical staining pattern that corresponds to the phenotype of interdigitating cells. Morphological and immunological implications of the abundant presence of these cells in pleomorphic adenomas are discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Abundant dendritic cells express HLA-DR in pleomorphic adenomas. 198 Jan 69

Using competition mobility shift, methylation interference, and proteolytic clipping DNA binding assays, we demonstrate that the protein binding the major histocompatibility complex A beta CCAAT box is indistinguishable from the protein previously named NF-Y, which binds the major histocompatibility complex E alpha CCAAT box. Although the two CCAAT boxes share the same 10-base core sequence, termed the Y box, their flanking sequences, known to be important for binding, are very different.
Mol Cell Biol 1991 Jan
PMID:The same CCAAT box-binding factor binds to the promoter of two coordinately regulated major histocompatibility complex class II genes. 198 50

Expression of major histocompatibility complex (MHC) class II antigens is a requirement for accessory cell function in antigen presentation. Recent reports have demonstrated the presence of class II antigens on human bronchial epithelial cells. In the present study, immunohistochemical staining revealed HLA-DR on human airway epithelial cells obtained from two different mucosal sites (lobar bronchus and nasal turbinates). To determine whether airway epithelial cells bear functional class II molecules that allow for their cognate interaction with T lymphocytes, cells isolated from these sites were used in mixed lymphocyte cultures (MLR), as an in vitro model of accessory cell function. Freshly isolated cells (11 bronchi/3 turbinates) stimulated allogeneic T lymphocytes (stimulation index [S.I.] = 9.3 [mean]; P less than 0.001 compared to T cells alone). In order to assess the potential role of contaminating conventional accessory cells, bronchial epithelial cell isolates were first preincubated in a serum-free, growth factor-supplemented medium that functionally eliminates potential non-epithelial stimulators prior to MLR culture. Conventional accessory cell-depleted epithelial cells were still capable of stimulating allogenic T lymphocytes in 18 of 23 MLR cultures (S.I. = 5.5 [mean]; P less than 0.0005 compared to T cells alone). The addition of an anti-class II monoclonal antibody (VG2.2) at the onset of culture completely inhibited the MLR response (n = 10). No shift in the CD4+/CD8+ ratio was detected between lymphocytes harvested from airway epithelial cell MLR (1.42 +/- 1.29) and the ratio from T lymphocytes cultured alone (1.3 +/- 0.75), suggesting that both CD4+ and CD8+ T lymphocytes were proliferating in response to stimulation from alloepitopes recognized on airway epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Apr
PMID:Evidence for accessory cell function by class II MHC antigen-expressing airway epithelial cells. 201 98

In order to determine how T cell-presented peptides associate with the antigen binding sites (desetopes) of class I major histocompatibility complex (MHC) molecules and how they might be scavenged from an endogenous processing pathway for transfer to those molecules, we characterized the binding of two synthetic peptides restricted by HLA-B37 or HLA-A2 to class I MHC molecules and to cellular proteins of histotyped cell lines, by gel filtration and photo-affinity labeling techniques. In gel filtration binding studies, each peptide associated with immunopurified class I MHC molecules from cells with its restricting, histotype, but little was bound to class I MHC molecules from cells without the restricting histotype and none was bound to bovine serum albumin. After crosslinkage of a radioiodinated photoreactive derivative of influenza virus nucleoprotein peptide NP(336-355Y) and immunoprecipitations with antibodies to class I MHC molecules, that peptide was found to bind to immunopurified class I MHC molecules from HLA-B37+ but not HLA-B37- cells. Binding of the [125I]NP peptide increased from 6 to 12 hr of incubation and was competed by unlabeled, NP peptide but not by HLA-A2-restricted, influenza virus matrix MA(57-73). The principal microsomal membrane proteins binding [125I]NP were about 65, 45 and 33 kD.
Mol Immunol
PMID:Binding of radioiodinated influenza virus peptides to class I MHC molecules and to other cellular proteins as analyzed by gel filtration and photoaffinity labeling. 206 16


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