dictyNews Volume 20 Number 01

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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. 

============= 
  Abstracts 
============= 

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]