This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Larsson, N.
Right arrow Articles by Gullberg, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larsson, N.
Right arrow Articles by Gullberg, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 1999, p. 2242-2250, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mutations of Oncoprotein 18/Stathmin Identify Tubulin-Directed Regulatory Activities Distinct from Tubulin Association

Niklas Larsson,1 Bo Segerman,1 Helena Melander Gradin,1 Ewa Wandzioch,1 Lynne Cassimeris,2 and Martin Gullberg1,*

Department of Cell and Molecular Biology, University of Umeå, Umeå, Sweden,1 and Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania2

Received 10 June 1998/Returned for modification 17 August 1998/Accepted 1 December 1998

Oncoprotein 18/stathmin (Op18) is a recently identified phosphorylation-responsive regulator of the microtubule (MT) system. It was originally proposed that Op18 specifically regulates dynamic properties of MTs by associating with tubulin, but it has subsequently been proposed that Op18 acts simply by sequestering of tubulin heterodimers. We have dissected the mechanistic action of Op18 by generation of two distinct classes of mutants. One class has interruptions of the heptad repeats of a potential coiled-coil region of Op18, and the other involves substitution at all four phosphorylation sites with negatively charged Glu residues. Both types of mutation result in Op18 proteins with a limited decrease in tubulin complex formation. However, the MT-destabilizing activities of the coiled-coil mutants are more severely reduced in transfected leukemia cells than those of the Glu-substituted Op18 derivative, providing evidence for tubulin-directed regulatory activities distinct from tubulin complex formation. Analysis of Op18-mediated regulation of tubulin GTPase activity and taxol-promoted tubulin polymerization showed that while wild-type and Glu-substituted Op18 derivatives are active, the coiled-coil mutants are essentially inactive. This suggests that Op18-tubulin contact involves structural motifs that deliver a signal of regulatory importance to the MT system.

* Corresponding author. Mailing address: Department of Cell and Molecular Biology, University of Umeå, S-901 87 Umeå, Sweden. Phone: 46 90 7852532. Fax: 46 90 771 420. E-mail: Martin.Gullberg{at}cmb.umu.se.

Molecular and Cellular Biology, March 1999, p. 2242-2250, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Honnappa, S., Cutting, B., Jahnke, W., Seelig, J., Steinmetz, M. O. (2003). Thermodynamics of the Op18/Stathmin-Tubulin Interaction. J. Biol. Chem. 278: 38926-38934 [Abstract] [Full Text]  
  • Brannstrom, K., Segerman, B., Gullberg, M. (2003). Molecular Dissection of GTP Exchange and Hydrolysis within the Ternary Complex of Tubulin Heterodimers and Op18/Stathmin Family Members. J. Biol. Chem. 278: 16651-16657 [Abstract] [Full Text]  
  • Amayed, P., Pantaloni, D., Carlier, M.-F. (2002). The Effect of Stathmin Phosphorylation on Microtubule Assembly Depends on Tubulin Critical Concentration. J. Biol. Chem. 277: 22718-22724 [Abstract] [Full Text]  
  • Holmfeldt, P., Larsson, N., Segerman, B., Howell, B., Morabito, J., Cassimeris, L., Gullberg, M. (2001). The Catastrophe-promoting Activity of Ectopic Op18/Stathmin Is Required for Disruption of Mitotic Spindles But Not Interphase Microtubules. Mol. Biol. Cell 12: 73-83 [Abstract] [Full Text]  
  • Larsson, N., Segerman, B., Howell, B., Fridell, K., Cassimeris, L., Gullberg, M. (1999). Op18/Stathmin Mediates Multiple Region-Specific Tubulin and Microtubule-Regulating Activities. JCB 146: 1289-1302 [Abstract] [Full Text]  
  • Segerman, B., Larsson, N., Holmfeldt, P., Gullberg, M. (2000). Mutational Analysis of Op18/Stathmin-Tubulin-interacting Surfaces. BINDING COOPERATIVITY CONTROLS TUBULIN GTP HYDROLYSIS IN THE TERNARY COMPLEX. J. Biol. Chem. 275: 35759-35766 [Abstract] [Full Text]  
  • Kuntziger, T., Gavet, O., Sobel, A., Bornens, M. (2001). Differential Effect of Two Stathmin/Op18 Phosphorylation Mutants on Xenopus Embryo Development. J. Biol. Chem. 276: 22979-22984 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»