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)

Deletion mutagenesis was used to identify sequences required for dimerization and enzymatic activity of the intracellular domain of the membrane guanylyl cyclase, GC-A. The intracellular domain of GC-A contains a protein kinase-like domain near its amino terminus, a guanylyl cyclase catalytic domain near its carboxyl terminus, and, between these domains, a region of unknown function predicted to form an amphipathic alpha-helix. Gel filtration analysis of deletion mutants of the GC-A intracellular domain suggested that a 43 amino acid sequence within the interdomain region was both necessary and sufficient for dimerization and was required for guanylyl cyclase catalytic activity. The ability of this sequence to mediate protein dimerization was confirmed in the yeast two-hybrid system, in which its fusion to the lexA DNA-binding domain and to the VP16 transcriptional activation domain led to their dimerization and consequent activation of a lexA-HIS3 gene. Thus, we have identified sequences responsible for dimerization of the intracellular domain of a guanylyl cyclase and shown that they are required for enzyme activity. Modulation of their interaction may be important in guanylyl cyclase activation.
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PMID:Identification of sequences mediating guanylyl cyclase dimerization. 771 74

Protein kinase-related domains of unknown function are present in the JAK family of protein tyrosine kinases and in receptor/guanylyl cyclases. I used the yeast two-hybrid system to screen for proteins interacting with the kinase-like domain of the atrial natriuretic peptide (ANP) receptor/guanylyl cyclase. A yeast strain was constructed expressing a fusion of this kinase-like domain to the lexA DNA-binding domain and containing a HIS3 gene under the control of lexA upstream activating sequences. These yeast cells were transformed with a plasmid library of mouse embryo cDNA fragments fused to the VP16 transcriptional activation domain. Cells containing VP16-fusion proteins interacting with the lexA-kinase-like domain fusion protein were selected by growth in the absence of histidine. A partial-length cDNA clone isolated by using this approach encoded a protein that interacted specifically with the ANP-receptor protein kinase-like domain both in yeast cells and in vitro. Tissue-specific expression of a 2.2-kb mRNA hybridizing to this cDNA paralleled the known pattern of ANP-receptor mRNA expression. A full-length cDNA clone isolated from a rat lung library was predicted to encode a 55-kDa protein containing at its amino terminus a targeting domain that binds to the ANP-receptor kinase-like domain and containing at its carboxyl terminus a putative protein-serine phosphatase domain. This protein is a possible candidate for the phosphatase involved in desensitizing the ANP receptor. Targeting of regulatory proteins may be an important function of protein kinase-like domains.
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PMID:Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor. 797 12