Published online May 26, 2008
doi:10.1083/jcb.200710111
The Journal of Cell Biology, Vol. 181, No. 5, 747-760
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Mondal et al.
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.

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