Protein kinase-phosphatase cascade

Surmeier DJ, Bargas J, Hemmings HC, Jr., Nairn AC, Greengard P (1995) Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. 

Brondello JM, Bnmet A, Pouyssegur J, McKenzie FR. The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are induced by the p42/p44MAPK cascade. J Biol Chem 1997 272 1368-1376. 

Phosphorylation by protein kinases of specific seryl, threonyl, or tyrosyl residues—and subsequent dephosphorylation by protein phosphatases—regulates the activity of many human enzymes. The protein kinases and phosphatases that participate in regulatory cascades which respond to hormonal or second messenger signals constimte a bio-organic computer that can process and integrate complex environmental information to produce an appropriate and comprehensive cellular response. 

Figure 1 The MAPK pathway and its connections to other signals A negative feedback loop connects the phosphorylated endpoint of the pathway ERK (Extracellular-signal Regulated Kinase) to the transcriptionally-driven synthesis of the phosphatase, MKP MAP kinase phosphatase. MKP then de-phosphorylates ERK to shut down the signaling cascade. The positive feedback loop again starts with the terminal kinase ERK which activates cPLA2 (cytosolic phospholipase A2). This leads to the synthesis of arachidonic acid, which, in turn activates protein kinase C (PKC). PKC is a positive regulator of RAS (Please see Color Plate Section in the back of this book).

Phosphoryl group transfer reactions add or remove phosphoryl groups to or from cellular metabolites and macromolecules, and play a major role in biochemistry. Phosphoryl transfer is the most common enzymatic function coded by the yeast genome and, in addition to its importance in intermediary metabolism (see Chapter 5), the reaction is catalysed by a large number of central regulatory enzymes that are often part of signalling cascades, such as protein kinases, protein phosphatases, ATPases and GTPases. 

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