This Article
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 Davis, J. N.
Right arrow Articles by Roussel, M. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davis, J. N.
Right arrow Articles by Roussel, M. F.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Dec 1997, 7398-7406, Vol 17, No. 12
Copyright © 1997, American Society for Microbiology

Complementation of growth factor receptor-dependent mitogenic signaling by a truncated type I phosphatidylinositol 4-phosphate 5-kinase

JN Davis, CO Rock, M Cheng, JB Watson, RA Ashmun, H Kirk, RJ Kay and MF Roussel
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Substitution of phenylalanine for tyrosine at codon 809 (Y809F) of the human colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) impairs ligand-stimulated tyrosine kinase activity, prevents induction of c-MYC and cyclin D1 genes, and blocks CSF-1-dependent progression through the G1 phase of the cell cycle. We devised an unbiased genetic screen to isolate genes that restore the ability of CSF-1 to stimulate growth in cells that express mutant CSF-1R (Y809F). This screen led us to identify a truncated form of the murine type Ibeta phosphatidylinositol 4-phosphate 5-kinase (mPIP5K-Ibeta). This truncated protein lacks residues 1 to 238 of mPIP5K-Ibeta and is catalytically inactive. When we transfected cells expressing CSF-1R (Y809F) with mPIP5K-Ibeta (delta1-238), CSF-1-dependent induction of c-MYC and cyclin D1 was restored and ligand-dependent cell proliferation was sustained. CSF-1 normally triggers the rapid disappearance of CSF-1R (Y809F) from the cell surface; however, transfection of cells with mPIP5K-Ibeta (delta1- 238) stabilized CSF-1R (Y809F) expression on the cell surface, resulting in elevated levels of ligand-activated CSF-1R (Y809F). These results suggest a role for PIP5K-Ibeta in receptor endocytosis and that the truncated enzyme compensated for a mitogenically defective CSF-1R by interfering with this process.


This article has been cited by other articles:

  • Lin, C.-W., Yan, F., Shimamura, S., Barg, S., Shyng, S.-L. (2005). Membrane Phosphoinositides Control Insulin Secretion Through Their Effects on ATP-Sensitive K+ Channel Activity. Diabetes 54: 2852-2858 [Abstract] [Full Text]  
  • Mirkin, S., Arslan, M., Churikov, D., Corica, A., Diaz, J.I., Williams, S., Bocca, S., Oehninger, S. (2005). In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum Reprod 20: 2104-2117 [Abstract] [Full Text]  
  • Winks, J. S., Hughes, S., Filippov, A. K., Tatulian, L., Abogadie, F. C., Brown, D. A., Marsh, S. J. (2005). Relationship between Membrane Phosphatidylinositol-4,5-Bisphosphate and Receptor-Mediated Inhibition of Native Neuronal M Channels. J. Neurosci. 25: 3400-3413 [Abstract] [Full Text]  
  • Rohde, C. M., Schrum, J., Lee, A. W.-M. (2004). A Juxtamembrane Tyrosine in the Colony Stimulating Factor-1 Receptor Regulates Ligand-induced Src Association, Receptor Kinase Function, and Down-regulation. J. Biol. Chem. 279: 43448-43461 [Abstract] [Full Text]  
  • Padron, D., Wang, Y. J., Yamamoto, M., Yin, H., Roth, M. G. (2003). Phosphatidylinositol phosphate 5-kinase I{beta} recruits AP-2 to the plasma membrane and regulates rates of constitutive endocytosis. JCB 162: 693-701 [Abstract] [Full Text]  
  • Barbieri, M. A., Heath, C. M., Peters, E. M., Wells, A., Davis, J. N., Stahl, P. D. (2001). Phosphatidylinositol-4-phosphate 5-Kinase-1beta Is Essential for Epidermal Growth Factor Receptor-mediated Endocytosis. J. Biol. Chem. 276: 47212-47216 [Abstract] [Full Text]  
  • Shyng, S.-L., Barbieri, A., Gumusboga, A., Cukras, C., Pike, L., Davis, J. N., Stahl, P. D., Nichols, C. G. (2000). Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase. Proc. Natl. Acad. Sci. USA 97: 937-941 [Abstract] [Full Text]  
  • Sorensen, S. D., Linseman, D. A., McEwen, E. L., Heacock, A. M., Fisher, S. K. (1999). Inhibition of beta 2-Adrenergic and Muscarinic Cholinergic Receptor Endocytosis after Depletion of Phosphatidylinositol Bisphosphate. J. Pharmacol. Exp. Ther. 290: 603-610 [Abstract] [Full Text]  
  • Cheng, M., Wang, D., Roussel, M. F. (1999). Expression of c-Myc in Response to Colony-stimulating Factor-1 Requires Mitogen-activated Protein Kinase Kinase-1. J. Biol. Chem. 274: 6553-6558 [Abstract] [Full Text]  
  • Achiriloaie, M., Barylko, B., Albanesi, J. P. (1999). Essential Role of the Dynamin Pleckstrin Homology Domain in Receptor-Mediated Endocytosis. Mol. Cell. Biol. 19: 1410-1415 [Abstract] [Full Text]  
  • Ward, A. C., van Aesch, Y. M., Schelen, A. M., Touw, I. P. (1999). Defective Internalization and Sustained Activation of Truncated Granulocyte Colony-Stimulating Factor Receptor Found in Severe Congenital Neutropenia/Acute Myeloid Leukemia. Blood 93: 447-458 [Abstract] [Full Text]  
  • Ishihara, H., Shibasaki, Y., Kizuki, N., Wada, T., Yazaki, Y., Asano, T., Oka, Y. (1998). Type I Phosphatidylinositol-4-phosphate 5-Kinases. CLONING OF THE THIRD ISOFORM AND DELETION/SUBSTITUTION ANALYSIS OF MEMBERS OF THIS NOVEL LIPID KINASE FAMILY. J. Biol. Chem. 273: 8741-8748 [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»