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dictyNews Volume 20 Number 01
Dicty News
Electronic Edition
Volume 20, number 1
January 18, 2003
Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to dicty@northwestern.edu.
Back issues of Dicty-News, the Dicty Reference database and other
useful information is available at DictyBase--http://dictybase.org.
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Abstracts
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Receptor Mediated Regulation of PI3Ks Confines PI(3,4,5)P3 to the
Leading Edge of Chemotaxing Cells
Yi Elaine Huang1, Miho Iijima1, Carole A. Parent,2 Satoru Funamoto3,
Richard A. Firtel3, and Peter Devreotes1
1Department of Cell Biology
Johns Hopkins University
School of Medicine
Baltimore, MD 21205
2Laboratory of Cellular and Molecular Biology
Division of Basic Sciences
NCI, NIH
37 Convent Drive, MSC 4255
Bldg. 37/Rm. 1E24
Bethesda, MD 20892-4255
3Section of Cell and Developmental Biology
Division of Biology
University of California, San Diego
9500 Gillman Drive
La Jolla, CA 92093
Molecular Biology of the Cell, In Press
Abstract
Recent studies have demonstrated that PH domains specific for
PI(3,4,5)P3 accumulate at the leading edge of a number of migrating
cells and that PI3Ks and PTEN associate with the membrane at the front
and back, respectively, of chemotaxing D. discoideum cells. However,
the dependence of chemoattractant induced changes in PI(3,4,5)P3 on PI3K
and PTEN activities have not been defined. We find that bulk PI(3,4,5)P3
levels increase transiently upon chemoattractant stimulation, and the
changes are greater and more prolonged in pten- cells. PI3K activation
increases within 5 seconds of chemoattractant addition and then declines
to a low level of activity identically in wild type and pten- cells.
Reconstitution of the PI3K activation profile can be achieved by mixing
membranes from stimulated pi3k1-/pi3k2- cells with cytosolic PI3Ks from
unstimulated cells. These studies show that significant control of
chemotaxis occurs upstream of the PI3Ks and that regulation of the PI3Ks
and PTEN cooperate to shape the temporal and spatial localization of
PI(3,4,5)P3.
submitted by Pam Antol [pjantol@jhmi.edu]
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Dictyostelium differentiation-inducing factor-3 activates glycogen synthase
kinase-3b and degrades cyclin D1 in mammalian cells
Fumi Takahashi-Yanaga, Yoji Taba, Yoshikazu Miwa, Yuzuru Kubohara, Yutaka
Watanabe, Masato Hirata, Sachio Morimoto, and Toshiyuki Sasaguri
Dept. of Clinical Pharmacology, Graduate school of Med. Sciences, Kyushu
University Dept. of Mol. Cell. Biochem., Graduate School of Dental Sciences,
Kyushu University, Fukuoka 812-8582 Biosignal Research Center, IMCR, Gunma
University, Mabashi 371-8512 Dept. of Applied Chem. Ehime University,
Matsuyama 790-8577, Japan
J. Biol. Chem. In press.
In search of chemical substances applicable for the treatment of cancer and
other proliferative disorders, we studied the signal transduction of
Dictyostelium differentiation-inducing factors (DIFs) in mammalian cells
mainly using HeLa cells. Although DIF-1 and DIF-3 both strongly inhibited
cell proliferation by inducing G0/G1 arrest, DIF-3 was more effective than
DIF-1. DIF-3 suppressed cyclin D1 expression at both mRNA and protein levels,
while the overexpression of cyclin D1 overrode DIF-3-induced cell cycle
arrest. The DIF-3-induced decrease in the amount of cyclin D1 protein
preceded the reduction in the level of cyclin D1 mRNA. The decrease in
cyclin D1 protein seemed to be caused by accelerated proteolysis, since
it was abrogated by ALLN, a proteasome inhibitor. DIF-3-induced degradation
of cyclin D1 was also prevented by treatment with lithium chloride, an
inhibitor of glycogen synthase kinase-3b (GSK-3b, suggesting that DIF-3
induced cyclin D1 proteolysis through the activation of GSK-3b. Indeed,
DIF-3 dephosphorylated Ser9 and phosphorylated tyrosine on GSK-3b, and it
stimulated GSK-3b activity in an in vitro kinase assay. Moreover, DIF-3
was revealed to induce the nuclear translocation of GSK-3b by
immunofluorescent microscopy and immunoblotting of subcellular protein
fractions. These results suggested that DIF-3 activates GSK-3b to
accelerate the proteolysis of cyclin D1 and this mechanism is involved in
the DIF-3-induced G0/G1 arrest in mammalian cells.
submitted by: kubohara@pop.showa.gunma-u.ac.jp
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[End Dicty News, volume 20, number 1]
