Recent developments in lymphocyte activation: linking kinases to downstream signaling events

The role of protein-protein interaction domains in signal transduction has been a topic of intensive study for the last ten years. Many of these studies have focused on the role of protein-protein interactions in signalling downstream of receptor and nonreceptor tyrosine kinases. However, recent evidence has pointed to the extensive role of protein-protein interaction domains in the localization and scaffolding of signaling molecules. In the continuation of this perspective series from the March 1999, no.6, issue, two articles discuss the role of protein-protein interactions in signalling downstream of tyrosine kinases. Clements and Koretzky highlight new insights into signaling by lymphocytes, while Virkamaki, Ueki, and Kahn examine the role of protein-protein interactions in insulin signaling and insulin resistance. In the previous issue, Schillace and Scott provided an overview of targeting in signal transduction by protein kinases and phosphatases, while Fanning and Anderson explored. PDZ domains, important for receptor targeting and clustering in a variety of cell systems.