Switching Signals On or Off by Receptor Dimerization

Many extracellular signals transduce their cellular responses by regulating the tyrosine phosphorylation of target proteins. Protein tyrosine kinases (PTKs) can be divided into two classes of enzymes: receptor PTKs that span a membrane, and cytoplasmic PTKs. Conversely, the dephosphorylation reaction of tyrosine phosphorylated proteins is carried out by protein tyrosine phosphatases (PTPs). PTPs can also be divided into two classes of enzymes: transmembrane receptor-like PTPs, and cytoplasmic PTPs. Considerable progress has been made in understanding the regulation and activation of PTKs. In contrast, very little is known about the regulation and activity of PTPs, although a few clues are emerging from recent structural and functional studies. Some of the paradigms learned from studying the PTKs have guided us well in our efforts toward understanding PTP function. However, some surprising differences are also suggested.