Protein phosphorylation metabolism

Group II assays consist of those monitoring cellular second messengers. Thus, activation of receptors to cause Gs-protein activation of adenylate cyclase will lead to elevation of cytosolic or extracellularly secreted cyclic AMP. This second messenger phosphorylates numerous cyclic AMP-dependent protein kinases, which go on to phosphorylate metabolic enzymes and transport and regulatory proteins (see Chapter 2). Cyclic AMP can be detected either radiometrically or with fluorescent probe technology. 

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. 

Haystead, T.A., et al.. Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism. Nature, 337, 6202, 78, 1989. 

Weller M (1979) Protein phosphorylation the nature, function, and metabolism of proteins with covalently bound phosphorus. Pion, London... 

Stimulation of NO synthase leads to activation of a NO-sensitive guanylyl cyclase. The associated increase in the cGMP level has multiple consequences. The cGMP can stimulate cGMP-dependent protein kinases it can also open cGMP-controUed ion channels. As a consequence, an increase in the intracellular Ca concentration takes place and a Ca signal is produced. NO can influence both protein phosphorylation and InsPs/diacylglycerol and Ca metabolism by this mechanism and activate a broad palette of biochemical reactions in the cell. 

In addition to regulation involving quantitative changes in protein levels, we have identified at least one apparent psi protein phosphorylation event (Fig. 7). This high molecular weight phosphoprotein appears early in Pi starvation and is not excreted into the medium. The function of this molecule in psi metabolism is unknown. 

The contraction of tracheal smooth muscle in response to carbacholamine [18-22] can be taken as an example of a system in which a temporal sequence of changes in the metabolism of inositol lipids, in Ca2+ metabolism, and in protein phosphorylation underlies cellular response (Fig. 4). Upon activation of the cell there is a transient rise in [Ca2+]c lasting 1-1.5 min which is followed by a transient rise in the content of MLC-P peaking in 3-5 min, and then declining to near basal values in 20-25 min. The development of force occurs simultaneously with the phosphoryl-... 

A. R Saltiel. The paradoxical regulation of protein phosphorylation in insulin action. FASEBJ, 8, (13), 1034-1040, 1994. Also J. A. Printen, M. J. Brady, A. R Saltiel. PTG, a protem phosphatase 1-binding protein with a role in glycogen metabolism. Science, T1S, 1475-1478, 1997. 

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