Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.1.14 (SPS)
 813 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

External supply of sucrose to carbon-starved Arabidopsis seedlings induced changes in phosphorylation of Brassinosteroid Signaling Kinase 8 (BSK8) at two different sites. Serine S(20) lies within a phosphorylation hotspot at the N-terminal region of the protein, while S(213) is located within the kinase domain of BSK8. Upon sucrose supply phosphorylation of BSK8(S20) and BSK8(S213) showed opposite behavior with increasing phosphorylation of S(213) and decreased phosphorylation of S(20) at 5 min after sucrose supply. Here we aim to systematically analyze the effects of BSK8 mutations on downstream cellular regulatory events and characterize molecular functions of BSK8 and its phosphorylation. Comparative phosphoproteomic profiling of a bsk8 knockout mutant and wild type revealed potential targets in sucrose metabolism. Activity of sucrose-phosphate synthase (SPS) was decreased by phosphorylation at S(152), and SPS phosphorylation inversely correlated with sucrose-induced BSK8 activity. Furthermore, BSK8 was found to interact with BSL2, a Kelch-type phosphatase. On the basis of a combination of kinase activity measurements, SPS activity assays, and phosphorylation site mutations in BSK8 at S(20) and S(213), we conclude that regulation of SPS by BSK8 occurs through activation of a phosphatase that in turn may dephosphorylate SPS and thus activates the enzyme.
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PMID:A kinase-phosphatase signaling module with BSK8 and BSL2 involved in regulation of sucrose-phosphate synthase. 2492 43

The ERK1 and ERK2 (ERK1/2) cascade is a central signaling pathway activated by a wide variety of extracellular agents that transmit the messages of G Protein Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs). Being such a central pathway, the activity of the cascade is well regulated, including by dynamic changes of the subcellular localization of components of the ERK1/2 cascade. In resting cells, ERK1/2 are localized in the cytosol due to their interactions with different anchoring proteins. After stimulation, ERK1/2 are phosphorylated by MEK1/2 on their regulatory TEY motif, which permits their detachment from the anchoring proteins. This detachment exposes ERK1/2 to additional phosphorylation on two serine residues (SPS motif) within the nuclear translocation signal (NTS) of the kinases. This additional phosphorylation allows ERK1/2 to interact with importin7, which consequently promotes their translocation to the nucleus. More studies are still required in order to better understand the mechanism and consequence of the nuclear translocation of ERK1/2. In this chapter, we describe some of the techniques used to study nuclear translocation of ERK1/2 in mammalian cells. We briefly mention methods such as digitonin permeabilization and cellular fractionation, as well as overexpression of reporter constructs. More thoroughly, we describe immunofluorescence, immunoprecipitation, and proximity ligation assay (PLA) approaches that are routinely used in our laboratory. Hopefully, the increase of knowledge based on these methods will open more opportunities for the identification of new therapeutic targets for diseases where the ERK1/2 cascade is dysregulated, such as cancer, neurodegenerative diseases, and diabetes.
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PMID:The Nuclear Translocation of ERK. 2792 67


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