Signal transduction eukaryotes

Airother interesting facet of lipid anchors is that they are transient. Lipid anchors can be reversibly attached to and detached from proteins. This provides a switching device for altering the affinity of a protein for the membrane. Reversible lipid anchoring is one factor in the control of signal transduction pathways in eukaryotic cells (Chapter 34). 

Researchers found that NAD serves as a substrate in poly(ADP-ribose) synthesis, a reaction important for DNA repair processes. In addition, it takes part in mono (ADP-ribosyl)ation reactions that are involved in endogenous regulation of many aspects of signal transduction and membrane trafficking in eukaryotic cells. 

Post-translational modification of proteins plays a critical role in cellular function. For, example protein phosphorylation events control the majority of the signal transduction pathways in eukaryotic cells. Therefore, an important goal of proteomics is the identification of post-translational modifications. Proteins can undergo a wide range of post-translational modifications such as phosphorylation, glycosylation, sulphonation, palmitoylation and ADP-ribosylation. These modifications can play an essential role in the function of the protein and mass spectrometry has been used to characterize such modifications. 

The mDHFR protein complementation assay has been used to map a signal transduction network that controls the initiation of translation in eukaryotes (Remy and Michnick, 2001). A total of 35 different pairs of full-length proteins were analyzed and 14 interactions were identified using the survival selection of cells grown in the absence of nucleotides. In addition, the use of the fMTX reagent in combination with fluorescence microscopy was used to localize the protein complex within cells (Remy and Michnick, 2001). 

Rhoads, R. E. (1999). Minireview Signal transduction pathways that regulate eukaryotic protein synthesis. J. Biol. Chem. 274, 30337-30340. 

Owing to their pivotal role in mammalian signal transduction, there has been an intense interest in the enzymes of the PLC superfamily. Progress toward understanding the mechanism, structure, and function of PI-PLCs from both bacterial and mammalian sources has been particularly impressive [12-15]. Several PI-PLCs have been isolated and cloned, and a number of high resolution, three-dimensional X-ray structures are available [16-19]. In contrast to the advances that have been made with mammalian PI-PLC isoenzymes, their PC-PLC counterparts are poorly characterized. Studies with mammalian PC-PLCs have typically been conducted with partially purified enzymes, and there has not been a report of the isolation of a pure, eukaryotic PC-PLC. To circumvent the currently intractable problems associated with mammalian PC-PLCs, PLCs from bacterial sources have been sought as potentially useful models. 

The family of eukaryotic Ras-like small GTPases may be divided into subfamilies, namely those of ARF, Rab, Ran, Ras, Rho, and Sar (ARF, RAB, RHO, RAS, RHO, SAR), which all contain representatives from fungi, plants, and metazoa. Consequently, these subfamilies and their cellular functions are likely to have emerged early in eukaryotic history. This implies that the last common ancestor of fungi, plants, and metazoa possessed vesicular transport (ARF and Sar), membrane trafficking (Rab), nuclear transport (Ran), signal transduction (Ras), and regulation of the actin cytoskeleton (Rho) functions. 

Eukaryotic ABC transport system Phosphotransferase system (PTS) Ion-coupled transport system Signal Transduction Two-component system Bacterial chemotaxis MAPK signaling pathway Second messenger signaling pathway Ligand-Receptor Interaction G-protein-coupled receptors Ion-channel-linked receptors Cytokine receptors Molecular Assembly Ribosome assembly Flagellar assembly Enzyme assembly... 

Phosphatidylinositol is synthesized by condensation of CDP-diacylglycerol with inositol (Fig. 21-26). Specific phosphatidylinositol kinases then convert phosphatidylinositol to its phosphorylated derivatives (see Fig. 10-17). Phosphatidylinositol and its phosphorylated products in the plasma membrane play a central role in signal transduction in eukaryotes (see Figs 12-8, 12-19). 

INHIBITION OF EUKARYOTE SIGNAL TRANSDUCTION COMPONENTS BY PLANT DEFENSIVE SECONDARY METABOLITES... 

As outlined above, protein phosphorylation is a key process involved in many signal transduction pathways and reversal of this process is catalyzed by a multiplicity of phosphoprotein phosphatases (PPs). Major PPs catalyzing dephosphorylation of phosphoserine or phosphothreonine residues on proteins include PP1 (inhibited by phosphorylated inhibitor protein I-1 and by okadaic acid and microsystins), PP2 (also inhibited by okadaic acid and microcystins), PP2B or calcineurin (CaM-activated and having a CaM-like regulatory subunit) and PP2C (Mg2+-dependent) [18]. These PPs have been found in all eukaryotes so far examined [18, 19]. In addition, a variety of protein phosphotyrosine phosphatases can reverse the consequences of RTK or JAK/STAT receptor activation [20]. 

With this sketch of major eukaryote signalling pathways in mind, we can now consider the interaction of particular plant defensive secondary metabolites with particular signal transduction components of non-plant eukaryotes such as fungi and animals that consume plants. The reader is referred to some major compilations for the structures of most of the plant defensive compounds mentioned [1,5,6]. 

Raetz, C.R.H. Bacterial endotoxins extraordinary lipids that activate eukaryotic signal transduction. J Bacteriol 175 (1993) 5745-5753. 

Raetz, C.R.H., Ulevitch, R.J., Wright, S.D., Sibley, C.H., Ding, A., Nathan, C.F. Gram-negative endotoxin an extraordinary lipid with profound effects on eukaryotic signal transduction. FASEB J 5 (1991) 2652-2660. 

---