![Figure][1] CREDIT: C. BICKEL/ SCIENCE The Science Perspectives and associated Connections Maps in the database of Cell Signaling at Science 's Signal Transduction Knowledge Environment ([www.sciencemag.org/sciext/cellsignaling06/][2]) highlight pathways initiated by three different types of receptors: brassinosteroid receptors that control plant size, G protein-coupled receptors that control mating responses in yeast, and Notch receptors that control cell fate in animals. Brassinosteroids are plant hormones that contribute to cell growth and division, differentiation, and reproductive development. As Belkhadir and Chory (p. [1410][3]) describe, the brassinosteroid receptor BR1 is a plasma membrane-localized leucine-rich-repeat receptor kinase that initiates a kinase cascade, ultimately controlling gene expression. Experiments in Arabidopsis thaliana have revealed that the active receptor complex is a serine-threonine kinase that initiates a process that inactivates BIN2, the plant homolog of glycogen synthase kinase 3 (GSK-3). Arabidopsis BIN2 is localized to the nucleus, whereas in animals, GSK-3 is cytosolic. BIM, which resembles the animal transcription factor Myc, interacts with the brassinosteroid response factor BES to enhance its activity. Thus, at each step of the brassinosteroid pathway—from the steroid hormone-like ligands to the transcription factors in the nucleus—there are similarities with animal pathways; however, no known pathway in animals assembles this cast of characters in quite the same way. Even well-characterized pathways continue to reveal new secrets. The yeast mating response is an extensively studied G protein-coupled receptor pathway, in which the G βγ subunits have been in the spotlight as the subunits that activate the mitogen-activated protein kinase cascade. Now, Slessareva and Dohlman (p. [1412][4]) describe how the Gα subunit participates in transmitting the mating signal by interacting with the phosphoinositide 3-kinase (PI3K) at the endosome to stimulate the production of phosphoinositide 3-phosphate. Not only was this a previously unknown function and location for Gγ in the yeast mating response, but the regulatory subunit of PI3K appears to serve as a noncanonical Gβ, subunit for the endosomally located Gα, a discovery that will undoubtedly stimulate a search for similar types of interactions in other systems. The Notch signaling pathway is crucial to animal development, and aberrant activity of this pathway is associated with certain types of leukemia. Ehebauer et al . (p. [1414][5]) explain how the transmembrane Notch receptor interacts with the transmembrane ligand on adjacent cells, which leads to cleavage and release of the Notch intracellular domain (NICD) that translocates to the nucleus and regulates gene expression. The cleavage of Notch remains an open area of research, with various candidates for the protease that performs the first cleavage in the extracellular domain and questions surrounding whether the second cleavage event occurs at the plasma membrane or after internalization. Notch acts in concert with other morphogenic signals to control cell fate; thus, understanding Notch signaling within the more complex signaling network remains a critical avenue of investigation. This knowledge may not only yield insight into animal development but also open the doors to new therapeutic opportunities in cases where the loss of differentiation contributes to disease. [1]: pending:yes [2]: http://www.sciencemag.org/sciext/cellsignaling06/ [3]: /lookup/doi/10.1126/science.1134040 [4]: /lookup/doi/10.1126/science.1134041 [5]: /lookup/doi/10.1126/science.1134042