Tyrosine Phosphatases in Cell Cycle and Transformation
The first part of this article is devoted to a historical overview of cellular regulation by protein phosphorylation. The field originated with a study of glycogen phosphorylase and the cascade system by which this enzyme can be activated. Reversible protein phosphorylation can be considered today as one of the most prevalent mechanism of control of biological systems. The second part will be devoted to protein tyrosine phosphatases (PTPs), an expanding family of intracellular and receptor-linked enzymes, and their involvement in cell cycle and transformation. Most transmembrane forms contain two catalytic domains but highly variable external segments. Likewise, the low Mr PTPs display a great variety of regulatory segments either preceding or following highly conserved catalytic domains. Deletion of the regulatory segment from a T-cell PTP and overexpression of the truncated enzyme in BHK cells results in multinucleation and asynchronous nuclear division. Furthermore, growth on soft agar and tumor formation in nude mice is inhibited. Similar results are obtained with rat-2 cells transformed with v-fms. The data indicate that, depending on the type of phosphatases involved and their localization within the cells, PTPs can act either synergistically or antagonistically with the tyrosine kinases to elicit a particular physiological response.
KeywordsAgar Carbohydrate Codon Tyrosine Serine
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