dictyNews
Electronic Edition
Volume 39, number 15
May 18, 2013
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Abstracts
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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 [[log in to unmask]]
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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 [[log in to unmask]]
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[End dictyNews, volume 39, number 15]
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