dictyNews Electronic Edition Volume 39, number 15 May 18, 2013 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. Follow dictyBase on twitter: http://twitter.com/dictybase ========= Abstracts ========= Xin-Hua Liao^, Jonathan Buggey+, Yun Kyung Lee, and Alan R. Kimmel* Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892-8028 Present Addresses: ^ Baylor College of Medicine, Houston, TX 77030 + School of Medicine, Georgetown University Washington, DC 20057 Molecular Biology of the Cell, in press Global stimulation of Dictyostelium with different chemoattractants elicits multiple transient signaling responses, including synthesis of cAMP and cGMP, actin polymerization, activation of kinases ERK2, TORC2, and PI3K, and Ras-GTP accumulation; mechanisms that down-regulate these responses are poorly understood. Here we examine transient activation of TORC2 in response to chemically distinct chemoattractants, cAMP and folate, and suggest that TORC2 is regulated by adaptive, de-sensitizing responses to stimulatory ligands that are independent of downstream, feedback or feed-forward circuits. Cells with acquired insensitivity to either folate or cAMP remain fully responsive to TORC2 activation if stimulated with the other ligand. Thus, TORC2 responses to cAMP or folate are not cross-inhibitory. Using a series of signaling mutants, we show that folate and cAMP activate TORC2 through an identical GEF/Ras pathway, but separate receptors and G protein couplings. Since the common GEF/Ras pathway also remains fully responsive to one chemoattractant after de-sensitization to the other, GEF/Ras must act downstream and independently of adaptation to persistent ligand stimulation. When initial chemoattractant concentrations are immediately diluted, cells rapidly regain full responsiveness. We suggest that ligand adaptation functions in upstream inhibitory pathways that involve chemoattractant-specific receptor/G protein complexes and regulate multiple response pathways. Submitted by Xin-Hua Liao [liaoxinhua@gmail.com] --------------------------------------------------------------------------- Novel Chlorinated Dibenzofurans Isolated from the Cellular Slime Mold, Polysphondylium filamentosum, and Their Biological Activities Authors: Haruhisa Kikuchi1,*, Yuzuru Kubohara2, Van Hai Nguyen1, Yasuhiro Katou1, and Yoshiteru Oshima1 1 Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan 2 Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan Bioorg. Med. Chem., in press. Cellular slime molds are expected to have the huge potential for producing secondary metabolites including polyketides, and we have studied the diversity of secondary metabolites of cellular slime molds for their potential utilization as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium filamentosum, we obtained new chlorinated benzofurans Pf-1 and Pf-2 which display multiple biological activities; these include stalk cell differentiation-inducing activity in the well- studied cellular slime mold, Dictyostelium discoideum, and inhibitory activities on cell proliferation in mammalian cells and gene expression in Drosophila melanogaster. Submitted by Haruhisa Kikuchi [hal@mail.pharm.tohoku.ac.jp] ============================================================== [End dictyNews, volume 39, number 15]