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 Kanagasundaram, V.
Right arrow Articles by Hamilton, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kanagasundaram, V.
Right arrow Articles by Hamilton, J. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 1999, p. 4079-4092, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Separation and Characterization of the Activated Pool of Colony-Stimulating Factor 1 Receptor Forming Distinct Multimeric Complexes with Signalling Molecules in Macrophages

V. Kanagasundaram,* A. Jaworowski,dagger R. Byrne, and J. A. Hamilton

Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia

Received 11 August 1998/Returned for modification 6 October 1998/Accepted 3 March 1999

Colony-stimulating factor 1 (CSF-1) triggers the activation of intracellular proteins in macrophages through selective assembly of signalling complexes. The separation of multimeric complexes of the CSF-1 receptor (CSF-1R) by anion-exchange chromatography enabled the enrichment of low-stoichiometry complexes. A significant proportion of the receptor in CSF-1-stimulated cells that neither possessed detectable tyrosine kinase activity nor formed complexes was separated from the receptor pool displaying autokinase activity that formed chromatographically distinct multimeric complexes. A small pool of CSF-1R formed a multimeric complex with phosphatidylinositol-3 kinase (PI-3 kinase), SHP-1, Grb2, Shc, c-Src, Cbl, and a significant number of tyrosine-phosphorylated proteins in CSF-1-stimulated cells. The complex showed a considerable amount of CSF-1R complex-associated kinase activity. A detectable level of the complex was also present in untreated cells. PI-3 kinase in the multimeric complex displayed low lipid kinase activity despite the association with several proteins. The major pool of activated CSF-1R formed transient multimeric complexes with distinctly different tyrosine-phosphorylated proteins, which included STAT3 but also PI-3 kinase, Shc, SHP-1, and Grb2. A significant level of lipid kinase activity was detected in PI-3 kinase in the latter complexes. The different specific enzyme activities of PI-3 kinase in these complexes support the notion that the activity of PI-3 kinase is modulated by its association with CSF-1R and other associated cellular proteins. Specific structural proteins associated with the separate CSF-1R multimeric complexes upon CSF-1 stimulation and the presence of the distinct pools of the CSF-1R were dependent on the integrity of the microtubular network.

* Corresponding author. Mailing address: Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Phone: (61 3) 93445478. Fax: (61 3) 93471863. E-mail: v.kanagasundaram{at}medicine.unimelb.edu.au.

dagger Present address: AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria 3078, Australia.

Molecular and Cellular Biology, June 1999, p. 4079-4092, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Liu, Y., Kruhlak, M. J., Hao, J.-J., Shaw, S. (2007). Rapid T cell receptor-mediated SHP-1 S591 phosphorylation regulates SHP-1 cellular localization and phosphatase activity. J. Leukoc. Biol. 82: 742-751 [Abstract] [Full Text]  
  • Yeung, Y.-G., Stanley, E. R. (2003). Proteomic Approaches to the Analysis of Early Events in Colony-stimulating Factor-1 Signal Transduction. Mol. Cell. Proteomics 2: 1143-1155 [Abstract] [Full Text]  
  • Bourgin, C., Bourette, R. P., Arnaud, S., Liu, Y., Rohrschneider, L. R., Mouchiroud, G. (2002). Induced Expression and Association of the Mona/Gads Adapter and Gab3 Scaffolding Protein during Monocyte/Macrophage Differentiation. Mol. Cell. Biol. 22: 3744-3756 [Abstract] [Full Text]  
  • Tilbrook, P. A., Palmer, G. A., Bittorf, T., McCarthy, D. J., Wright, M. J., Sarna, M. K., Linnekin, D., Cull, V. S., Williams, J. H., Ingley, E., Schneider-Mergener, J., Krystal, G., Klinken, S. P. (2001). Maturation of Erythroid Cells and Erythroleukemia Development Are Affected by the Kinase Activity of Lyn. Cancer Res. 61: 2453-2458 [Abstract] [Full Text]  
  • Lai, C.-C., Henningson, C., DiMaio, D. (2000). Bovine Papillomavirus E5 Protein Induces the Formation of Signal Transduction Complexes Containing Dimeric Activated Platelet-derived Growth Factor beta Receptor and Associated Signaling Proteins. J. Biol. Chem. 275: 9832-9840 [Abstract] [Full Text]  
  • Murray, J, Wilson, L, Kellie, S (2000). Phosphatidylinositol-3' kinase-dependent vesicle formation in macrophages in response to macrophage colony stimulating factor. J. Cell Sci. 113: 337-348 [Abstract]  


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