Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A wide variety of mechanisms have evolved for intercellular communication in metazoans, but some of the signaling molecules were already used in their predecessors. The social amoeba, Dictyostelium discoideum, is known to use peptides to trigger sporulation within fruiting bodies, but their sequences have not been defined. We found that the peptide signal spore differentiation factor 2 (SDF-2) is processed from acyl-CoA binding protein, AcbA. The mammalian homolog of AcbA is processed to diazepam binding inhibitor that binds to the GABA(A) receptor in the brain and to peripheral 1,4 benzodiazepine receptors. Although Dictyostelium has neither GABA(A) nor peripheral-type benzodiazepine receptors, we find that both a diazepam binding inhibitor peptide and diazepam (Valium) can mimic SDF-2 in a Dictyostelium bioassay. Mutants lacking AcbA sporulate well only when developed in chimeras with WT cells. Using a yeast system we show that ligand binding to the SDF-2 receptor histidine kinase, DhkA, inhibits phosphorelay, which can account for its ability to induce rapid sporulation.
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PMID:Peptide signaling during terminal differentiation of Dictyostelium. 1589 58

The social amoeba Dictyostelium discoideum diverged from the line leading to animals shortly after the separation of plants and animals but it retained characteristics of both kingdoms. A GABA(B)-like receptor and a peptide, SDF-2, with homologs found only in animals, control sporulation, while cytokinins, which act as hormones in plants, keep spores dormant. When SDF-2 binds its receptor DhkA, it reduces the activity of the cAMP phosphodiesterase RegA such that cAMP levels can increase. It has been proposed that the cytokinin discadenine also produces in an increase in cAMP but acts through a different histidine kinase, DhkB. We have found that discadenine and its precursor, isopentenyl adenine, not only maintain spore dormancy but also initiate rapid encapsulation independently of the SDF-2 signal transduction pathway. DhkB and the adenylyl cyclase of late development, AcrA, are members of two component signal transduction families and both are required to transduce the cytokinin signal. As expected, strains lacking the isopentenyl-transferase enzyme chiefly responsible for cytokinin synthesis are defective in sporulation. It appears that SDF-2 and cytokinins are secreted during late development to trigger signal transduction pathways that lead to an increase in the activity of the camp-dependent protein kinase, PKA, which triggers rapid encapsulation as well as ensuring spore dormancy.
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PMID:Cytokinins induce sporulation in Dictyostelium. 1821 68