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 Vedham, V.
Right arrow Articles by Coggeshall, K. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vedham, V.
Right arrow Articles by Coggeshall, K. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2005, p. 4211-4220, Vol. 25, No. 10
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.10.4211-4220.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Vav Activation and Function as a Rac Guanine Nucleotide Exchange Factor in Macrophage Colony-Stimulating Factor-Induced Macrophage Chemotaxis

Vidya Vedham,1,2 Hyewon Phee,4 and K. Mark Coggeshall1,2,3*

The Oklahoma Medical Research Foundation, Immunobiology and Cancer Program, 825 N.E. 13th St., Oklahoma City, Oklahoma 73104,1 Departments of Microbiology and Immunology,2 Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma,3 Department of Medicine, University of California, San Francisco, San Francisco, California4

Received 12 November 2004/ Returned for modification 28 December 2004/ Accepted 16 February 2005

Signal transduction mediated by phosphatidylinositol 3-kinase (PI 3-kinase) is regulated by hydrolysis of its products, a function performed by the 145-kDa SH2 domain-containing inositol phosphatase (SHIP). Here, we show that bone marrow macrophages of SHIP–/– animals have elevated levels of phosphatidylinositol 3,4,5-trisphosphate [PI (3,4,5)P3] and displayed higher and more prolonged chemotactic responses to macrophage colony-stimulating factor (M-CSF) and elevated levels of F-actin relative to wild-type macrophages. We also found that the small GTPase Rac was constitutively active and its upstream activator Vav was constitutively phosphorylated in SHIP–/– macrophages. Furthermore, we show that Vav in wild-type macrophages is recruited to the membrane in a PI 3-kinase-dependent manner through the Vav pleckstrin homology domain upon M-CSF stimulation. Dominant inhibitory mutants of both Rac and Vav blocked chemotaxis. We conclude that Vav acts as a PI 3-kinase-dependent activator for Rac activation in macrophages stimulated with M-CSF and that SHIP regulates macrophage M-CSF-triggered chemotaxis by hydrolysis of PI (3,4,5)P3.

* Corresponding author. Mailing address: The Oklahoma Medical Research Foundation, Immunobiology and Cancer Program, 825 N.E. 13th St., Oklahoma City, OK 73104. Phone: (405) 271-7905. Fax: (405) 271-8568. E-mail: mark-coggeshall{at}omrf.ouhsc.edu.

Molecular and Cellular Biology, May 2005, p. 4211-4220, Vol. 25, No. 10
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.10.4211-4220.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Luo, Y., Isaac, B. M., Casadevall, A., Cox, D. (2009). Phagocytosis Inhibits F-Actin-Enriched Membrane Protrusions Stimulated by Fractalkine (CX3CL1) and Colony-Stimulating Factor 1. Infect. Immun. 77: 4487-4495 [Abstract] [Full Text]  
  • Malhotra, S., Kovats, S., Zhang, W., Coggeshall, K. M. (2009). B Cell Antigen Receptor Endocytosis and Antigen Presentation to T Cells Require Vav and Dynamin. J. Biol. Chem. 284: 24088-24097 [Abstract] [Full Text]  
  • Spurrell, D. R., Luckashenak, N. A., Minney, D. C., Chaplin, A., Penninger, J. M., Liwski, R. S., Clements, J. L., West, K. A. (2009). Vav1 Regulates the Migration and Adhesion of Dendritic Cells. J. Immunol. 183: 310-318 [Abstract] [Full Text]  
  • Sindrilaru, A., Peters, T., Schymeinsky, J., Oreshkova, T., Wang, H., Gompf, A., Mannella, F., Wlaschek, M., Sunderkotter, C., Rudolph, K. L., Walzog, B., Bustelo, X. R., Fischer, K. D., Scharffetter-Kochanek, K. (2009). Wound healing defect of Vav3-/- mice due to impaired {beta}2-integrin-dependent macrophage phagocytosis of apoptotic neutrophils. Blood 113: 5266-5276 [Abstract] [Full Text]  
  • Mehta, H., Glogauer, M., Becart, S., Altman, A., Coggeshall, K. M. (2009). Adaptor Protein SLAT Modulates Fc{gamma} Receptor-mediated Phagocytosis in Murine Macrophages. J. Biol. Chem. 284: 11882-11891 [Abstract] [Full Text]  
  • Baran, C. P., Opalek, J. M., McMaken, S., Newland, C. A., O'Brien, J. M. Jr., Hunter, M. G., Bringardner, B. D., Monick, M. M., Brigstock, D. R., Stromberg, P. C., Hunninghake, G. W., Marsh, C. B. (2007). Important Roles for Macrophage Colony-stimulating Factor, CC Chemokine Ligand 2, and Mononuclear Phagocytes in the Pathogenesis of Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 176: 78-89 [Abstract] [Full Text]  
  • Faccio, R., Takeshita, S., Colaianni, G., Chappel, J., Zallone, A., Teitelbaum, S. L., Ross, F. P. (2007). M-CSF Regulates the Cytoskeleton via Recruitment of a Multimeric Signaling Complex to c-Fms Tyr-559/697/721. J. Biol. Chem. 282: 18991-18999 [Abstract] [Full Text]  
  • Zhao, T., Nalbant, P., Hoshino, M., Dong, X., Wu, D., Bokoch, G. M. (2007). Signaling requirements for translocation of P-Rex1, a key Rac2 exchange factor involved in chemoattractant-stimulated human neutrophil function. J. Leukoc. Biol. 81: 1127-1136 [Abstract] [Full Text]  
  • Cho, Y. J., Cunnick, J. M., Yi, S.-J., Kaartinen, V., Groffen, J., Heisterkamp, N. (2007). Abr and Bcr, Two Homologous Rac GTPase-Activating Proteins, Control Multiple Cellular Functions of Murine Macrophages. Mol. Cell. Biol. 27: 899-911 [Abstract] [Full Text]  
  • Zhuang, G., Hunter, S., Hwang, Y., Chen, J. (2007). Regulation of EphA2 Receptor Endocytosis by SHIP2 Lipid Phosphatase via Phosphatidylinositol 3-Kinase-dependent Rac1 Activation. J. Biol. Chem. 282: 2683-2694 [Abstract] [Full Text]  
  • Schymeinsky, J., Sindrilaru, A., Frommhold, D., Sperandio, M., Gerstl, R., Then, C., Mocsai, A., Scharffetter-Kochanek, K., Walzog, B. (2006). The Vav binding site of the non-receptor tyrosine kinase Syk at Tyr 348 is critical for beta2 integrin (CD11/CD18)-mediated neutrophil migration. Blood 108: 3919-3927 [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»