Cell signaling by protein tyrosine phosphorylation.
The above data, and others not described herein, indicate the following: First, that phosphatases are not scavenger enzymes, simply there to remove the phosphate groups introduced by the kinases. They cannot be viewed simply as providing an 'off' switch in an 'on/off' kinase/phosphatase system. Kinases and phosphatases do not carry out one-way and opposing reactions. The same enzyme, depending on where it localizes within the cell, or the molecule with which it might interact, can serve either as a positive or negative determinant in defining cell behavior. In many instances, it can act synergistically with the kinases to enhance the phosphorylation reaction. Second, the factors that determine whether a phosphatase would enhance or oppose a kinase reaction would seem to depend less on its state of activity than on its subcellular localization. This would suggest that if one wanted to call upon it to control transformation, one should try to tamper with its localization segments or whatever binding proteins it might be attached to--rather than with its catalytic domains. Displacement of these enzymes from where they are meant to bind would seem a more promising approach than trying to modulate their catalytic activity. Finally, their architectural features are so basically different from those of the kinases, with receptor tyrosine phosphatases displaying all the structural characteristics of cell adhesion molecules, that they must also have a mission of their own in cell development, survival and death, quite apart from that of the kinases.
Fischer
E H
EH
Department of Biochemistry, University of Washington, Seattle, USA.
D000818:Animals; D002471:Cell Transformation, Neoplastic; D006801:Humans; D009154:Mutation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases