V. Conclusion

Phosphorylation is a versatile post translational modification which is a recurrent theme for regulation of the activity not only of individual enzymes but of entire signal transduction pathways.

X-ray crystallographic studies on the structures of both the inactive form and the active form of phosphorylase provides insight into the mechanism of activation due to phosphorylation. The only other enzyme for which both the phosphorylated and unphosphorylated structure has been investigated by x-ray crystallography is isocitrate dehydrogenase. However, unlike phosphorylase, the phosphorylation of isocitrate dehydrogenase inactivates the enzyme.

The glycogenolysis pathway illustrates the amplification of the extracellular hormonal signal glucagon via the mediation of the intracellular second messenger cAMP. cAMP in turn activates the phosphorylation/dephosphorylation reactions which results in the conversion of inactive phosphorylase b to active phosphorylase a catalyzing the degradation of glycogen.

In the glycogenolysis pathway, the cell surface receptor is classified as a G protein-linked receptor. Other small molecules such as epinephrine and serotinin function in a similar manner to glucagon, binding to G protein-linked receptors and transducing signals using a second messenger and phosphorylation.

Phosphorylation is employed as a mechanism of signal transduction in the cytokine-receptor superfamily where ligand binding causes the receptor to dimerize, activating the cytosolic tyrosine kinases. Examples from this family include cytokines, interferons and human growth hormone.

An area of very active investigation is the role of phosphorylation in modulating nuclear events such as the cell cycle and gene transcription. These limited examples serve to illustrate only a subset of the variety of effects that result upon protein phosphorylation. The chemical nature of the phosphoryl group and the facile reaction catalyzed by the kinases and phosphatases makes phosphorylation ubiquitous and invaluable in cellular regulatory processes.