Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways.
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PMID:Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion. 128 78

Autoantibodies against the cardiac beta-adrenoceptor are present in 30-40% of patients with idiopathic dilated cardiomyopathy and can be detected using ligand binding inhibition, immunoprecipitation or immunoblotting. The functional consequences of the antibody-receptor interactions are two-fold: (a) in isolated cardiac myocytes, diluted sera from cardiomyopathy patients induce internalization of the beta-receptors which are subsequently degraded intracellularly; (b) in membrane preparations, anti-receptor antibodies inhibit selectively the activity of isoproterenol-sensitive adenylate cyclase. The presence of anti-receptor antibodies is strongly linked to the HLA-DR4 phenotype: 72% of the HLA-DR4 patients in our series had anti-beta-receptor antibodies compared with 22% of the HLA-DR4-negative patients (most of which typed as HLA-DR1). Conversely, 67% of the antibody-positive patients typed as HLA-DR4, compared with only 10% of the antibody-negative patients. These results indicate the presence, in a subset of cardiomyopathy patients, of immunogenetical factors which may modulate myocardial beta-adrenoceptor function.
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PMID:Beta-adrenoceptor antibodies and genetics in dilated cardiomyopathy--an overview and review. 165 46

Autoantibodies against the cardiac beta 1-adrenoceptor are present in the sera of patients with idiopathic dilated cardiomyopathy and may modulate the responsiveness of cardiac beta-adrenergic pathways to agonists. The regulation of cardiac adenylate cyclase activity by autoantibodies was examined in 50 patients with dilated cardiomyopathy. Inhibition of isoproterenol-sensitive adenylate cyclase activity could be demonstrated by serum dilutions or IgG in 52% (26 of 50) of the patients; basal and NaF-stimulated activities, in contrast, were unaffected. In 14 patients, both ligand binding to beta-receptor and isoproterenol-sensitive adenylate cyclase activity were inhibited by 100-fold serum dilutions. Pretreatment of cardiac membranes with pertussis toxin did not affect inhibition of adenylate cyclase indicating that the effect of sera does not depend on Gi. The immunogenetic control of antireceptor antibodies was examined by comparing the distribution of HLA antigens in antibody-positive and antibody-negative patients. HLA-DR4 and HLA-DR1 were strongly associated with antibodies inhibiting ligand binding and adenylate cyclase activity (71% of patients with such antibodies typed as either DR4 or DR1). Conversely 58% of patients with HLA-DR4 and 71% of patients with HLA-DR1 antibodies showed inhibition of adenylate cyclase activity compared to 46% of those who lacked both HLA-DR4 and HLA-DR1 antibodies. These results strongly suggest that cardiac beta-adrenergic receptors and adenylate cyclase activity in dilated cardiomyopathy can be modulated by circulating autoantibodies, the presence of which is under the control of the major histocompatibility complex.
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PMID:Influence of anti-beta-receptor antibodies on cardiac adenylate cyclase in patients with idiopathic dilated cardiomyopathy. 216 38

The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assay and adenylate cyclase stimulation, and the HLA alleles was studied in 41 patients with Hashimoto's thyroiditis. TSH binding-inhibiting immunoglobulins (TBII) were detected in 9 (22%) patients, and human thyroid adenylate cyclase-stimulating immunoglobulins (HTACS) were found in 21 (51%) patients. Only 2 patients were positive in both assays, and an inverse relationship was observed between TBII and HTACS. In the 21 HTACS-positive patients, HLA-Dw5 was only found in 1 subject, compared to 8 of the 20 HTACs-negative patients (P less than 0.01), while 4 of the 9 TBII-positive patients had HLA-Dw5 compared to 5 of the 32 TBII-negative subjects (P = -0.09). No significant relations were observed between the presence of HTACS or TBII and HLA-Dw3 or HLA-B8. It is concluded, that TBII and HTACS are produced independently in Hashimoto's thyroiditis, and that the production of these autoantibodies seems to be related to the HLA-D region in this disease.
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PMID:Thyroid-stimulating immunoglobulins in Hashimoto's thyroiditis measured by radioreceptor assay and adenylate cyclase stimulation and their relationship to HLA-D alleles. 612 90