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Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999.

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Cover of Basic Neurochemistry

Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition.

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Tyrosine Phosphorylation in the Nervous System

and .

Correspondence to Richard L. Huganir, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, 904A PCTB, Baltimore, Maryland 21205.

Protein phosphorylation is one of the most important mechanisms in the regulation of cellular functions. Proteins can be phosphorylated on serine, threonine or tyrosine residues. Most phosphorylation occurs on serine and threonine, with less than 1% on tyrosine. This perhaps accounts for the late discovery of tyrosine phosphorylation, which was found first on polyoma virus middle T antigen in 1979 by Hunter and colleagues [1]. Since then, a growing number of proteins have been shown to be tyrosine-phosphorylated. Originally, tyrosine phosphorylation was believed to be involved primarily in regulating cell proliferation since many oncogene products and growth factor receptors are protein tyrosine kinases (PTKs) [2]. However, it is clear that tyrosine phosphorylation is involved in regulating a variety of cellular processes. In fact, the nervous system contains large amounts of PTKs and protein tyrosine phosphatases (PTPs) [3], and some of these are exclusively expressed in neuronal tissues. For example, Figure 25-1 shows the immunocytochemical staining of a cultured hippocampal neuron with an antiphosphotyrosine antibody [4]. It reveals the presence of tyrosine-phosphorylated proteins in the cell body as well as synapses and suggests that tyrosine phosphorylation plays a role in neuronal function. Furthermore, many neuronal processes are affected by PTK or PTP inhibitors and by deletion of genes encoding for PTKs and PTPs.

Figure 25-1. Phosphotyrosine staining of a hippocampal neuron.

Figure 25-1

Phosphotyrosine staining of a hippocampal neuron. A cultured rat hippocampal pyramidal neuron is stained with an antiphosphotyrosine antibody and detected by a secondary antibody conjugated to rhodamine. The staining reflects the presence of tyrosine-phosphorylated (more...)

Tyrosine phosphorylation is controlled by a balance of the activity between PTKs and PTPs (Fig. 25-2). PTKs catalyze the transfer of the γ-phosphate from ATP to its substrate, while PTPs remove phosphate from phosphotyrosine (Fig. 25-2). Phosphorylation of a tyrosine residue changes a polar environment to a negatively charged one. It also increases the size of the tyrosine side chain. These changes consequently elicit a change in the structure of the substrate protein, altering its function. Alternatively, the phosphotyrosine sequence becomes a molecular adhesive which can change the subcellular distribution of the tyrosine-phosphorylated protein or interacting proteins, initiating assembly of signal-transduction complexes.

Figure 25-2. Tyrosine phosphorylation and dephosphorylation.

Figure 25-2

Tyrosine phosphorylation and dephosphorylation. Protein tyrosine kinases (PTKs) catalyze the transfer of the γ-phosphate group from ATP to the hydroxyl group of tyrosine residues, whereas protein tyrosine phosphatases (PTPs) remove the phosphate (more...)

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 1999, American Society for Neurochemistry.
Bookshelf ID: NBK28192


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