Protein phosphorylation reversible

SPECIFIC PROTEIN PHOSPHORYLATION (REVERSED BY PROTEIN PHOSPHATASES)... 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

Marine algae transform arsenate into nonvolatile methylated arsenic compounds such as methanearsonic and dimethylarsinic acids (Tamaki and Frankenberger 1992). Freshwater algae and macrophytes, like marine algae, synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Terrestrial plants preferentially accumulate arsenate over arsenite by a factor of about 4. Phosphate inhibits arsenate uptake by plants, but not the reverse. The mode of toxicity of arsenate in plants is to partially block protein synthesis and interfere with protein phosphorylation — a process that is prevented by phosphate (Tamaki and Frankenberger 1992). 

Reversible protein phosphorylation occurs by means of protein kinases. Eukaryotic protein kinases comprise a 250-amino acid, conserved catalytic domain. They are widely exploited in the regulation of physiological processes according to estimates the mammalian genome contains over 2000 PK genes. 

Lhcbl was the first Lhc cDNA identified and sequenced [52, 53]. Since then sequences have been made available from 20 species (for a review see [54]) Lhcbl is present in many copies in the genome ranging from 5 in Arabidopsis [55] to 16 in Petunia [29]. The mature protein consist of 232 amino acids starting with an acetylated Arginine residue [56]. However small differences exist between species and between different Lhcb genes within the same specie thus yielding multiple Lhcbl polypeptides [26]. The protein is reversibly phosphorylated at a threonine residue close to N-terminal [33, 57]. 

The simultaneous activities of the kinase and phosphatase are yet another example of regnlation by reversible protein phosphorylation (i.e. an interconversion cycle -Chapter 3). An increased force of contraction could be caused either by inhibition of the phosphatase or by activation of the kinase. However, physiologically relevant inhibitors of the phosphatase have not yet been discovered. 

Many proteins undergo reversible phosphorylation that is a major mechanism for regulation of protein function (see Chapter 14). 

Glycogen synthase is regulated via the same pathway. Glycogen synthase is inactive in the phosphorylated form whereas in the dephosphorylated form, it is active. Three key enzymes of glycogen metabohsm are thus controlled with the help of reversible protein phosphorylation. 

Protein phosphatase I that has dissociated from glycogen may be inactivated by association with inhibitor proteins, preventing undesired dephosphorylation of proteins in the cytosol. The activity of inhibitor proteins may in turn be controlled by reversible phosphorylation. A hormone-induced activation of protein kinase A leads to phosphorylation of inhibitor protein 1 the phosphorylated form is the active form of the inhibitor. This mechanism ensures that stimulation of protein phosphorylation mediated by cAMP and protein kinase A is not weakened by an opposing dephosphorylation (Fig. 7.17). 

S cr-ketobutyrate -i- phosphorylated histidine-containing protein <6> (Reversibility <6> [15]) [15]... 

Barford, D. (1999) Structural studies of reversible protein phosphorylation and protein phosphatases. Biochem. Soc. Trans. 27, 751-766. 

Edmond H. Fischer and Edwin G. Krebs Physiology/Medicine Reversible protein phosphorylation in biological regulation... 

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]. 

Protein phosphorylation alters protein ligand binding and/or catalytic functions and hence specific cellular processes, this representing the cellular response to the stimulus of the original primary messenger . The signalling system must be reversible and the protein phosphorylation step of the stimulus-response pathway is reversed through the action of phosphoprotein phosphatases (PPs), which are phosphohydrolases that catalyse the hydrolytic dephosphorylation of proteins ... 

Recently, several studies suggested that protein nitration could be a cellular signaling mechanism and is often a reversible and selective process, similar to protein phosphorylation (Aulak et al., 2004 Koeck et al., 2004). In addition, modified proteins are believed to be either degraded or subject to processes that could lead to enzymatic denitration (Gow et al., 1996 Kamisaki et al., 1998 Me et al., 2003). The latter possibility is intriguing because this would allow the process of tyrosine nitration to be reversible and thus enable a more dynamic physiological role. Protein nitration is observed under normal conditions in all tissues. In AD brain levels of nitrated proteins were found to be increased compared to that of control (Smith et al.. 

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