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Published online
doi:10.1083/jcb.200710111
The Journal of Cell Biology, Vol. 181, No. 5, 747-760
The Rockefeller University Press, 0021-9525 $30.00
© Mondal et al.
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Article

Linking Ras to myosin function: RasGEF Q, a Dictyostelium exchange factor for RasB, affects myosin II functions



Subhanjan Mondal1, Deenadayalan Bakthavatsalam1, Paul Steimle2, Berthold Gassen1, Francisco Rivero1,3, and Angelika A. Noegel1

1 Centre for Biochemistry, Institute of Biochemistry I, Medical Faculty and Centre for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany
2 Department of Biology, University of North Carolina at Greensboro, Greensboro, NC 27402
3 The Hull York Medical School and Department of Biological Sciences, University of Hull, HU6 7RX Hull, England, UK

Correspondence to Angelika A. Noegel: noegel{at}uni-koeln.de

Ras guanine nucleotide exchange factor (GEF) Q, a nucleotide exchange factor from Dictyostelium discoideum, is a 143-kD protein containing RasGEF domains and a DEP domain. We show that RasGEF Q can bind to F-actin, has the potential to form complexes with myosin heavy chain kinase (MHCK) A that contain active RasB, and is the predominant exchange factor for RasB. Overexpression of the RasGEF Q GEF domain activates RasB, causes enhanced recruitment of MHCK A to the cortex, and leads to cytokinesis defects in suspension, phenocopying cells expressing constitutively active RasB, and myosin-null mutants. RasGEF Q mutants have defects in cell sorting and slug migration during later stages of development, in addition to cell polarity defects. Furthermore, RasGEF Q mutants have increased levels of unphosphorylated myosin II, resulting in myosin II overassembly. Collectively, our results suggest that starvation signals through RasGEF Q to activate RasB, which then regulates processes requiring myosin II.

D. Bakthavatsalam's present address is Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005.

Abbreviations used in this paper: DIAS, Dynamic Image Analysis software; GEF, guanine nucleotide exchange factor; GPCR, G protein–coupled receptor; LatA, latrunculin A; LB, lysis buffer; MHCK, myosin II heavy chain kinase; pI, isoelectric point; RBD, ras binding domain; RTK, receptor tyrosine kinase.

© 2008 Mondal et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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