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)

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

Brassinosteroids, which control plant growth and development, are sensed by the membrane receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1). Brassinosteroid binding to the BRI1 leucine-rich repeat (LRR) domain induces heteromerisation with a SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK)-family co-receptor. This process allows the cytoplasmic kinase domains of BRI1 and SERK to interact, trans-phosphorylate and activate each other. Here we report crystal structures of the BRI1 kinase domain in its activated form and in complex with nucleotides. BRI1 has structural features reminiscent of both serine/threonine and tyrosine kinases, providing insight into the evolution of dual-specificity kinases in plants. Phosphorylation of Thr1039, Ser1042 and Ser1044 causes formation of a catalytically competent activation loop. Mapping previously identified serine/threonine and tyrosine phosphorylation sites onto the structure, we analyse their contribution to brassinosteroid signaling. The location of known genetic missense alleles provide detailed insight into the BRI1 kinase mechanism, while our analyses are inconsistent with a previously reported guanylate cyclase activity. We identify a protein interaction surface on the C-terminal lobe of the kinase and demonstrate that the isolated BRI1, SERK2 and SERK3 cytoplasmic segments form homodimers in solution and have a weak tendency to heteromerise. We propose a model in which heterodimerisation of the BRI1 and SERK ectodomains brings their cytoplasmic kinase domains in a catalytically competent arrangement, an interaction that can be modulated by the BRI1 inhibitor protein BKI1.
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PMID:Crystal structures of the phosphorylated BRI1 kinase domain and implications for brassinosteroid signal initiation. 2446 62

Phytosulfokine (PSK) belongs to the group of plant peptide growth factors. It is a disulfated pentapeptide encoded by precursor genes that are ubiquitously present in higher plants, suggestive of universal functions. Processing of the preproprotein involves sulfonylation by a tyrosylprotein sulfotransferase in the trans-golgi and proteolytic cleavage in the apoplast. The secreted peptide is perceived at the cell surface by a membrane-bound receptor kinase of the leucine-rich repeat family. The PSK receptor PSKR1 from Arabidopsis thaliana is an active kinase and has guanylate cyclase activity resulting in dual-signal outputs. Receptor activity is regulated by calmodulin. While PSK may be an autocrine growth factor, it also acts non-cell autonomously by promoting growth of cells that are receptor-deficient. In planta, PSK has multiple functions. It promotes cell growth, acts in the quiescent centre cells of the root apical meristem, contributes to funicular pollen tube guidance, and differentially alters immune responses depending on the pathogen. It has been suggested that PSK integrates growth and defence signals to balance the competing metabolic costs of these responses. This review summarizes our current understanding of PSK synthesis, signalling, and activity.
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PMID:Phytosulfokine peptide signalling. 2575 6

Phytosulfokine (PSK) is perceived by the leucine-rich repeat receptor kinase PSKR1 and promotes growth in Arabidopsis thaliana. PSKR1 is coexpressed with the CYCLIC NUCLEOTIDE-GATED CHANNEL gene CNGC17. PSK promotes protoplast expansion in the wild type but not in cngc17. Protoplast expansion is likewise promoted by cGMP in a CNGC17-dependent manner. Furthermore, PSKR1-deficient protoplasts do not expand in response to PSK but are still responsive to cGMP, suggesting that cGMP acts downstream of PSKR1. Mutating the guanylate cyclase center of PSKR1 impairs seedling growth, supporting a role for PSKR1 signaling via cGMP in planta. While PSKR1 does not interact directly with CNGC17, it interacts with the plasma membrane-localized H(+)-ATPases AHA1 and AHA2 and with the BRI-associated receptor kinase 1 (BAK1). CNGC17 likewise interacts with AHA1, AHA2, and BAK1, suggesting that PSKR1, BAK1, CNGC17, and AHA assemble in a functional complex. Roots of deetiolated bak1-3 and bak1-4 seedlings were unresponsive to PSK, and bak1-3 and bak1-4 protoplasts expanded less in response to PSK but were fully responsive to cGMP, indicating that BAK1 acts in the PSK signal pathway upstream of cGMP. We hypothesize that CNGC17 and AHAs form a functional cation-translocating unit that is activated by PSKR1/BAK1 and possibly other BAK1/RLK complexes.
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PMID:Phytosulfokine Regulates Growth in Arabidopsis through a Response Module at the Plasma Membrane That Includes CYCLIC NUCLEOTIDE-GATED CHANNEL17, H+-ATPase, and BAK1. 2607 21

We examined the genes encoding the proteins that mediate the Ca-feedback regulatory system in vertebrate rod and cone phototransduction. These proteins comprise four families: recoverin/visinin, the guanylyl cyclase activating proteins (GCAPs), the guanylyl cyclases (GCs) and the sodium/calcium-potassium exchangers (NCKXs). We identified a paralogon containing at least 36 phototransduction genes from at least fourteen families, including all four of the families involved in the Ca-feedback loop (recoverin/visinin, GCAPs, GCs and NCKXs). By combining analyses of gene synteny with analyses of the molecular phylogeny for each of these four families of genes for Ca-feedback regulation, we have established the likely pattern of gene duplications and losses underlying the expansion of isoforms, both before and during the two rounds of whole-genome duplication (2R WGD) that occurred in early vertebrate evolution. Furthermore, by combining our results with earlier evidence on the timing of duplication of the visual G-protein receptor kinase genes, we propose that specialization of proto-vertebrate photoreceptor cells for operation at high and low light intensities preceded the emergence of rhodopsin, which occurred during 2R WGD.
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PMID:Evolution of the calcium feedback steps of vertebrate phototransduction. 3025 95

Plant pathogens secrete cell wall-degrading enzymes that degrade various components of the plant cell wall. Plants sense this cell wall damage as a mark of infection and induce immune responses. However, the plant functions that are involved in the elaboration of cell wall damage-induced immune responses remain poorly understood. Transcriptome analysis revealed that a rice (Oryza sativa) receptor-like kinase, WALL-ASSOCIATED KINASE-LIKE21 (OsWAKL21.2), is up-regulated following treatment with either Xanthomonas oryzae pv oryzae (a bacterial pathogen) or lipaseA/esterase (LipA; a cell wall-degrading enzyme of X. oryzae pv oryzae). Overexpression of OsWAKL21.2 in rice induces immune responses similar to those activated by LipA treatment. Down-regulation of OsWAKL21.2 attenuates LipA-mediated immune responses. Heterologous expression of OsWAKL21.2 in Arabidopsis (Arabidopsis thaliana) also activates plant immune responses. OsWAKL21.2 is a dual-activity kinase that has in vitro kinase and guanylate cyclase activities. Interestingly, kinase activity of OsWAKL21.2 is necessary to activate rice immune responses, whereas in Arabidopsis, OsWAKL21.2 guanylate cyclase activity activates these responses. Our study reveals a rice receptor kinase that activates immune responses in two different species via two different mechanisms.
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PMID:Dual Activities of Receptor-Like Kinase OsWAKL21.2 Induce Immune Responses. 3235 78