Focus Issue: Protein Interactions Domains, the Second Set

Abstract

Science's STKE continues to feature the structural motifs important in cellular signaling processes in a second focus issue on the theme of protein interaction domains. The first issue featured an overview published in Science by Pawson and Nash describing signaling domains and their function. STKE featured three Reviews. Lasko described proteins implicated in cellular signaling that have RNA binding motifs, thus linking posttranscriptional regulatory mechanisms to cellular signaling events. Zarrinpar et al . highlighted the domains that recognize proline-rich motifs complete with animations to allow STKE readers to appreciate the differences in binding mechanisms. Finally, Nourry et al . discussed the biological and medical relevance of proteins that contain PDZ domains, a motif that serves as a scaffold to organize multimolecular structures. The second issue in this series features two more interaction motifs: those that recognize phosphorylated tyrosine residues and those that form a β-propeller structure. In the Review by Schlessinger and Lemmon, the spotlight is on the Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains. Not only do they describe the structural features and differences in the binding characteristics of these motifs, but they also provide an overview of their roles in cellular signaling processes. SH2 and PTB domains play crucial roles in regulating protein localization, assembly, and activation and contribute to the regulation of many cellular processes in response to external signals. In the Perspective by Gettemans et al ., the spotlight is on two highly divergent classes of proteins, based on primary sequence, that show very similar overall structure. Gettemans et al . describe proteins with either WD-40 repeats or kelch repeats that adopt the β-propeller structure. These results are described in the context of yeast G protein-signaling cascades. By folding into a β propeller similar to that seen for the G protein β subunit, kelch-domain proteins may function as one subunit of the heterotrimeric G protein in place of the β subunit in particular signaling cascades. The results in yeast emphasize the importance of structure over sequence similarity and open a new avenue for exploring G protein partners and interactions. The final element to this second domains issue is the unveiling of a new section of the STKE site: Teaching Resources. In the Teaching Resources section, you will find various teaching and learning resources that can be used for academic educational purposes. This section will grow to become a collection of resources either developed during the publishing of STKE original articles or Connections Maps or resources contributed by the scientific community. Each resource developed by the STKE will have the scientific oversight of the scientist contributing the article or serving as the Pathway Authority and resources submitted by the community will be reviewed for scientific accuracy. In addition, many STKE articles, Connections Maps, and Teaching Resources will be indexed in the BioSciEdNet portal ( ), an index of peer-reviewed educational resources from the digital libraries at various scientific societies. The first item to be added to the STKE Teaching Resources is an animation created with Zarrinpar et al . that shows schematically how SH3 domains contribute to protein activation using the activation of Ras by the Grb2-SOS complex as an example. As always, the STKE editors welcome your comments, suggestions, and criticisms. The Teaching Resources section, as well as the ST on the Web and Events sections, has a special feedback form that allows users to nominate resources for inclusion in these various sections. Featured in This Focus Issue Reviews Perspectives Teaching Resources Related Resources at STKE Editorial Guides ST on the Web