Control of cell activation by phosphatases

Phosphatases constitute a group of enzymes which are distinguished by their cellular expression, their substrate specificity, as well as their function in the cellular homeostasis. Phosphatases can be expressed as transmembrane proteins, involved in cell adhesion, differentiation and/or cell migration. Phosphatases can also be cytosolic enzymes primarily involved in cell signal transduction. Among the members of the vast phosphatase family, protein tyrosine phosphatases (PTP) regulate the level of protein phosphorylation on tyrosine residues in concert with the reciprocal enzymes, protein tyrosine kinases (PTK). Tyrosine phosphorylation is a post-transcriptional modification which affects the intracytoplasmic domain of integral receptors as well as cytosolic molecules mainly involved in signal transduction pathways. Regulation of signal transduction ensured by SH2-domain containing phosphatases is of special interest. These protein tyrosine phosphatases control signal transduction downstream of various cell surface receptors and can act positively or negatively, either by dephosphorylating critical tyrosine residues or by acting as adaptor molecules. Taken together, these observations suggest that cells display a large variety of strategies based on phosphatases, which allow a fine tuning between activatory and inhibitory pathways.