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.
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