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 Wilhelmsen, K.
Right arrow Articles by van der Geer, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilhelmsen, K.
Right arrow Articles by van der Geer, P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2004, p. 454-464, Vol. 24, No. 1
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.1.454-464.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Phorbol 12-Myristate 13-Acetate-Induced Release of the Colony-Stimulating Factor 1 Receptor Cytoplasmic Domain into the Cytosol Involves Two Separate Cleavage Events

Kevin Wilhelmsen and Peter van der Geer*

Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093-0601

Received 27 June 2003/ Returned for modification 30 July 2003/ Accepted 30 September 2003

The colony-stimulating factor 1 (CSF-1) receptor is a protein-tyrosine kinase that regulates cell division, differentiation, and development. In response to phorbol 12-myristate 13-acetate (PMA), the CSF-1 receptor is subject to proteolytic processing. Use of chimeric receptors indicates that the CSF-1 receptor is cleaved at least two times, once in the extracellular domain and once in the transmembrane domain. Cleavage in the extracellular domain results in ectodomain shedding while the cytoplasmic domain remains associated with the membrane. Intramembrane cleavage depends on the sequence of the transmembrane domain and results in the release of the cytoplasmic domain. This process can be blocked by {gamma}-secretase inhibitors. The cytoplasmic domain localizes partially to the nucleus, displays limited stability, and is degraded by the proteosome. CSF-1 receptors are continuously subject to down-modulation and regulated intramembrane proteolysis (RIP). RIP is stimulated by granulocyte-macrophage-CSF, CSF-1, interleukin-2 (IL-2), IL-4, lipopolysaccharide, and PMA and may provide the CSF-1 receptor with an additional mechanism for signal transduction.

* Corresponding author. Mailing address: Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0601. Phone: (858) 822-2024. Fax: (858) 822-0079. E-mail: geer{at}ucsd.edu.

Molecular and Cellular Biology, January 2004, p. 454-464, Vol. 24, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.1.454-464.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kaimori, J.-y., Nagasawa, Y., Menezes, L. F., Garcia-Gonzalez, M. A., Deng, J., Imai, E., Onuchic, L. F., Guay-Woodford, L. M., Germino, G. G. (2007). Polyductin undergoes notch-like processing and regulated release from primary cilia. Hum Mol Genet 16: 942-956 [Abstract] [Full Text]  
  • Liu, C.-X., Ranganathan, S., Robinson, S., Strickland, D. K. (2007). {gamma}-Secretase-mediated Release of the Low Density Lipoprotein Receptor-related Protein 1B Intracellular Domain Suppresses Anchorage-independent Growth of Neuroglioma Cells. J. Biol. Chem. 282: 7504-7511 [Abstract] [Full Text]  
  • Pozner-Moulis, S., Pappas, D. J., Rimm, D. L. (2006). Met, the Hepatocyte Growth Factor Receptor, Localizes to the Nucleus in Cells at Low Density. Cancer Res. 66: 7976-7982 [Abstract] [Full Text]  
  • Becker-Herman, S., Arie, G., Medvedovsky, H., Kerem, A., Shachar, I. (2005). CD74 Is a Member of the Regulated Intramembrane Proteolysis-processed Protein Family. Mol. Biol. Cell 16: 5061-5069 [Abstract] [Full Text]  
  • Arasada, R. R., Carpenter, G. (2005). Secretase-dependent Tyrosine Phosphorylation of Mdm2 by the ErbB-4 Intracellular Domain Fragment. J. Biol. Chem. 280: 30783-30787 [Abstract] [Full Text]  
  • Singh, A. J., Meyer, R. D., Band, H., Rahimi, N. (2005). The Carboxyl Terminus of VEGFR-2 Is Required for PKC-mediated Down-Regulation. Mol. Biol. Cell 16: 2106-2118 [Abstract] [Full Text]  
  • Wilhelmsen, K., Copp, J., Glenn, G., Hoffman, R. C., Tucker, P., van der Geer, P. (2004). Purification and Identification of Protein-Tyrosine Kinase-binding Proteins Using Synthetic Phosphopeptides as Affinity Reagents. Mol. Cell. Proteomics 3: 887-895 [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»