Classical Anticytokinins Do Not Interact with Cytokinin Receptors but Inhibit Cyclin-dependent Kinases

Abstract

Cytokinins are a class of plant hormones that regulate the cell cycle and diverse developmental and physiological processes. Several compounds have been identified that antagonize the effects of cytokinins. Based on structural similarities and competitive inhibition, it has been assumed that these anticytokinins act through a common cellular target, namely the cytokinin receptor. Here, we examined directly the possibility that various representative classical anticytokinins inhibit the Arabidopsis cytokinin receptors CRE1/AHK4 (cytokinin response 1/Arabidopsis histidine kinase 4) and AHK3 (Arabidopsis histidine kinase 3). We show that pyrrolo Cytokinins are plant hormones that play essential roles in the regulation of various aspects of plant growth and development (1). They include a variety of chemicals with different degrees of structural similarity, some of which occur naturally in plants, and others that are known only as synthetic compounds. The natural cytokinins are adenine derivatives that can be classified according to the nature of their N 6 -side chain as either isoprenoid (zeatin) or aromatic (benzyladenine) cytokinins.Cytokinins are key regulators of the plant cell cycle, and the induction of cell division is considered diagnostic for this class of plant hormones. The molecular basis of this activity is only partially understood and may differ in different cell types. Cytokinins have been found to control tyrosine dephosphorylation and activation of p34 cdc2 -like H1 histone kinase (2), as well as the transcriptional activation of cyclin D3 (3). Some of the many physiological and developmental processes that are controlled by cytokinin, such as the formation and activity of shoot apical meristems, floral development, the breaking of bud dormancy, and seed germination (4 -8), are at least in part functionally linked to cell cycle control.Recently, several cytokinin receptors were identified in Arabidopsis (9 -12) and Zea mays (13). To date, three cytokinin receptors have been identified in Arabidopsis, AHK2, 4 AHK3, and CRE1/AHK4. All are membrane-located sensor histidine kinases with a predicted extracellular ligand-binding domain and cytoplasmic His kinase and receiver domains. It has been shown that the cytokinin signal is transmitted by a multistep phospho-relay system through a complex form of the two-component signaling pathway that has long been known in prokaryotes and lower eukaryotes. Among higher eukaryotes, the two-component signaling pathway is only found in plants (reviewed by Refs. 14 -17).

Eternal Youth, the Fate of Developing Arabidopsis Leaves uponRhodococcus fasciansInfection

“…The main virulence factors of R. fascians are the fas-encoded cytokinins (Crespi et al, 1992(Crespi et al, , 1994Vereecke et al, 2000;Pertry et al, 2009). Because cytokinins are known to directly regulate cell division at the G2-to-M transition by dephosphorylating CDKs (Zhang et al, 1996(Zhang et al, , 2005Laureys et al, 1998;Spíchal et al, 2007), besides stimulating CDKB1;1 expression, the direct activation of CDKs by the bacterial cytokinins might represent a second level of stimulation at the G2/M checkpoint.…”

When Cytokinin, a Plant Hormone, Meets the Adenosine A2A Receptor: A Novel Neuroprotectant and Lead for Treating Neurodegenerative Disorders?

“…Later, Froldi et al [9] showed that 6-benzyladenine could act on a purinergic type-2 receptor that induces calcium mobilization in rat atria, suggesting a membrane-bound protein for cytokinins in animal cells. In addition, since cytokinins are important at specific phases of the plant cell cycle [10], in parallel, their anticancer effects were attributed to mediation by cyclins [11] or cyclin-dependent kinases [12], [13], suggesting the potential for cytokinins as anticancer drugs [7]. Thus, cytokinin might be used as a plant hormone and also could possibly serve as a candidate for treating human diseases.…”

High Throughput Screening Method for Identifying Potential Agonists and Antagonists of Arabidopsis thaliana Cytokinin Receptor CRE1/AHK4

“…In the presented method the validation step is based on the direct confirmation of the hit interaction with the ligand-binding site. However, whatever cytokinin-specific bioassay can be used for the further functional validation of a cytokinin receptor agonist or antagonist as described, e.g., by Doležal et al (2006) and Spíchal et al (2007), respectively.…”