Protein kinase activity sensors

Sharma, V., Wang, Q. and Lawrence, D. S. (2008). Peptide-based fluorescent sensors of protein kinase activity Design and applications. Biochim Biophys. Acta. 1784, 94—99. 

Kikuchi K, Hashimoto S, Mizukami S et al (2009) Anion sensor-based ratiometric peptide probe for protein kinase activity. Org Lett 11 2732-2735... 

Real-Time and Continuous Sensors of Protein Kinase Activity Utilizing Chelation-Enhanced Fluorescence... 

Martin K et al. (2003) Quantitative analysis of protein phosphorylation status and protein kinase activity on microarrays using a novel fluorescent phosphorylation sensor dye. Proteomics 3 1244-1255... 

Hardie DG, Hawley SA, Scott JW (2006) AMP-activated protein kinase - development of the energy sensor concept. J Physiol 574 7-15... 

The two-component pathway is characterized by two functional elements. A histidine-specific protein kinase functions as a sensor that registers an external signal and passes this on to a downstream response regulator. The latter is activated by phosphorylation during the process of signal transduction, triggering other reactions in the cell (Fig. 12.3). 

Fig. 12.4. Example of a two-component pathway in S. cerevisiae. Model of signal transdnction via the SLNl protein. The SLNl protein is a transmembrane protein with two transmembrane elements, which is assumed to exist as a dimer. The sensor domain and the regulator domain are localized on the same protein chain in the SLNl protein. The SLNl protein is activated by an extracellular signal (e.g., decrease in osmolarity). Autophosphorylation takes place on His (H) in the sensor domain and on Asp (D) in the regulator domain. A phosphate transfer takes place from the phosphohisti-dine to the effector protein SSKl. In the unphosphory-lated form, SSKl activates a MAPK pathway, which contains the protein kinase HOGl as a MAPK element. Various cellular reactions are triggered by HOGL If SSKl is phosphorylated in the course of activation of the two-component pathway, stimulation of the MAPK pathway is stopped. According to Swanson et al., (1994).

Glutamate-mediated Ca2+ entry through NMDA at the plasma membrane level and mobilization of Ca2+from intracellular stores through PLC-mediated generation of PtdIns-3/J is indispensable for the basal NF-kB activity. Three cytosolic Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p2 l(ras)/phosphatidylinositol 3-kinase (Ptdlns-3K)/Akt pathways, are simultaneously involved in the steps linking the Ca2+ to NF-kB activity (Lilienbaum and Israel, 2003 Marchetti et al., 2004 Lubin et al., 2005). Calmodulin modulates calcineurin, a Ca2+-dependent protein phosphatase, which plays a role in the basal NF-kB activity, whilst stimulation of both the calmodulin kinase II and Akt kinase pathways results in the up-regulation of the transcriptional potential of the p65 subunit of NF-/cB (Lilienbaum and Israel,... 

In primary cultures of neonatal cerebellar granule neurons, all Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p21(ras)/phosphatidylinositol 3 -kinase (Ptdlns-3K)/Akt pathway, converge towards NF-kB at the levels of nuclear translocation as well as transcription. The duration of NF-kB activation is a critical determinant for sensitivity toward excitotoxic stress and is dependent on the different upstream and downstream signaling associated with various kinases. This is in contrast to studies in non-neuronal cells, which either do not respond to Ca2+ or do not simultaneously activate all three cascades (Lilienbaum and Israel, 2003). Collective evidence suggests that brain inflammatory processes differ from systemic inflammation not only in the involvement of various types of neural cells but also in differences in response to second messengers. 

Hardie, D. G., Carling, D. and Carlson, M., 1998, The AMP-activated/SNFl protein kinase subfamily metabolic sensors of the eukaryotic cell , Annu Rev Biochem, 67, pp 821—55. 

McAllister CS, Samuel CE (2009) The RNA-activated protein kinase enhances the induction of interferon-beta and apoptosis mediated by cytoplasmic RNA sensors. J Biol Chem 284 1644-1651... 

Chaki S, Muramatsu M, Otomo S (1994) Involvement of protein kinase C activation in regulation of acetylcholine release from rat hippocampal slices by minaprine. Neurochem Int 24 37-41 Chameau P, Van d, V, Fossier P et al (2001) Ryanodine-, IP3- and NAADP-dependent calcium stores control acetylcholine release. Pflugers Arch 443 289-96 Chapman ER (2002) Synaptotagmin a Ca(2+) sensor that triggers exocytosis Nat Rev Mol Cell Biol 3 498-508... 

Hardie, D. G. 2003. Minireview the AMP-activated protein kinase cascade the key sensor of cellular energy status. Endocrinology 144 5179-5183. 

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