Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cloned ANF-sensitive guanylyl cyclase (GC-A) and ANF-sensitive guanylyl cyclase from adrenal cortex differ in their sensitivity to the ANF analogs atriopeptin 1 and urodilatin. To test the hypothesis that these differences are due to different glycosylation, we investigated the effect of the N-glycosylation inhibitor tunicamycin on GC-A. Tunicamycin altered the response of GC-A to atriopeptin 1 and urodilatin, whereas the sensitivity to ANF remained unchanged. These data indicate that agonist specificities of different ANF-sensitive guanylyl cyclases are influenced by carbohydrate moieties.
 ...
PMID:Effect of glycosylation on cloned ANF-sensitive guanylyl cyclase. 876 Oct 9

Inhibition of constitutive nitric oxide (cNO) production inhibits SGLT1 activity by a reduction in the affinity for glucose without a change in Vmax in intestinal epithelial cells (IEC-18). Thus, we studied the intracellular pathway responsible for the posttranslational modification/s of SGLT1. NO is known to mediate its effects via cGMP which is diminished tenfold in L-NAME treated cells. Inhibition of cGMP production at the level of guanylyl cyclase or inhibition of protein kinase G also showed reduced SGLT1 activity demonstrating the involvement of PKG pathway in the regulation of SGLT1 activity. Metabolic labeling and immunoprecipitation with anti-SGLT1 specific antibodies did not show any significant changes in phosphorylation of SGLT1 protein. Tunicamycin to inhibit glycosylation reduced SGLT1 activity comparable to that seen with L-NAME treatment. The mechanism of inhibition was secondary to decreased affinity without a change in Vmax. Immunoblots of luminal membranes from tunicamycin treated or L-NAME treated IEC-18 cells showed a decrease in the apparent molecular size of SGLT1 protein to 62 and 67 kD, respectively suggesting an alteration in protein glycosylation. The deglycosylation assay with PNGase-F treatment reduced the apparent molecular size of the specific immunoreactive band of SGLT1 from control and L-NAME treated IEC-18 cells to approximately 62 kD from their original molecular size of 75 kD and 67 kD, respectively. Thus, the posttranslational mechanism responsible for the altered affinity of SGLT1 when cNO is diminished is secondary to altered glycosylation of SGLT1 protein. The intracellular pathway responsible for this alteration is cGMP and its dependent kinase.
 ...
PMID:Regulation of sodium glucose co-transporter SGLT1 through altered glycosylation in the intestinal epithelial cells. 2441 19

C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. Immunofluorescence microscopy also indicated that the mutant receptors were on the cell surface. All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism.
...
PMID:Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism. 2447 69