The CDPK-SnRK superfamily consists of seven types of serine-threonine protein kinases: calcium-dependent protein kinase (CDPKs), CDPK-related kinases (CRKs), phosphoenolpyruvate carboxylase kinases (PPCKs), PEP carboxylase kinase-related kinases (PEPRKs), calmodulin-dependent protein kinases (CaMKs), calcium and calmodulin-dependent protein kinases (CCaMKs), and SnRKs. Within this superfamily, individual isoforms and subfamilies contain distinct regulatory domains, subcellular targeting information, and substrate specificities. Our analysis of the Arabidopsis genome identified 34 CDPKs, eight CRKs, two PPCKs, two PEPRKs, and 38 SnRKs. No definitive examples were found for a CCaMK similar to those previously identified in lily (Lilium longiflorum) and tobacco (Nicotiana tabacum) or for a CaMK similar to those in animals or yeast. CDPKs are present in plants and a specific subgroup of protists, but CRKs, PPCKs, PEPRKs, and two of the SnRK subgroups have been found only in plants. CDPKs and at least one SnRK have been implicated in decoding calcium signals in Arabidopsis. Analysis of intron placements supports the hypothesis that CDPKs, CRKs, PPCKs and PEPRKs have a common evolutionary origin; however there are no conserved intron positions between these kinases and the SnRK subgroup. CDPKs and SnRKs are found on all five Arabidopsis chromosomes. The presence of closely related kinases in regions of the genome known to have arisen by genome duplication indicates that these kinases probably arose by divergence from common ancestors. The PlantsP database provides a resource of continuously updated information on protein kinases from Arabidopsis and other plants.In eukaryotes, protein kinases are involved in regulating key aspects of cellular function, including cell division, metabolism, and responses to external signals. The completed sequence of the Arabidopsis genome provides the first opportunity to identify all of the protein kinases present in a model plant. The Arabidopsis genome encodes 1,085 typical protein kinases (M. Gribskov, unpublished data), which is about 4% of the predicted 25,500 genes (Arabidopsis Article, publication date, and citation information can be found at www.plantphysiol.org/cgi
Recent studies report that two types of El Niñ o events have been observed. One is the cold tongue (CT) El Niñ o, which is characterized by relatively large sea surface temperature (SST) anomalies in the eastern Pacific, and the other is the warm pool (WP) El Niñ o, in which SST anomalies are confined to the central Pacific. Here, both types of El Niñ o events are analyzed in a long-term coupled GCM simulation. The present model simulates the major observed features of both types of El Niñ o, incorporating the distinctive patterns of each oceanic and atmospheric variable. It is also demonstrated that each type of El Niñ o has quite distinct dynamic processes, which control their evolutions. The CT El Niñ o exhibits strong equatorial heat discharge poleward and thus the dynamical feedbacks control the phase transition from a warm event to a cold event.On the other hand, the discharge process in the WP El Niñ o is weak because of its spatial distribution of ocean dynamic field. The positive SST anomaly of WP El Niñ o is thermally damped through the intensified evaporative cooling.
IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6–stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6–dependent TF-1 cell proliferation. LMT-28 antagonized IL-6–induced TNF-α production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6Rα, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6Rα complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.
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