Emerging issues in receptor protein tyrosine phosphatase function: liftingfog or simply shifting?

Transmembrane (receptor) tyrosine phosphatases are intimately involved in r esponses to cell-cell and cell-matrix contact. Several important issues reg arding the targets and regulation of this protein family are now emerging. For example, these phosphatases exhibit complex interactions with signaling pathways involving SRC family kinases, which result from their ability to control phosphorylation of both activating and inhibitory sites in these ki nases and possibly also their substrates. Similarly, integrin signaling ill ustrates how phosphorylation of a single protein, or the activity of a path way, can be controlled by multiple tyrosine phosphatases, attesting to the intricate integration of these enzymes in cellular regulation. Lastly, we a re starting to appreciate the roles of intracellular topology, tyrosine pho sphorylation and oligomerization among the many mechanisms regulating tyros ine phosphatase activity.