Organization of kinases, phosphatases, and receptor signaling complexes

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 signaling 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. This Perspective series reviews the role of protein‐protein interactions in localization and downstream signaling. The first Perspective in the series, by Schillace and Scott, provides an overview of targeting in signal transduction by protein kinases and phosphatases. The second in this issue, by Fanning and Anderson, explores PDZ domains, important for receptor targeting and clustering in a variety of cell systems. This series continues in the April 1999, no. 7, issue; two Perspectives discuss the role of protein‐protein interactions in signaling 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.