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 Gu, Y.
Right arrow Articles by Williams, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gu, Y.
Right arrow Articles by Williams, D. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2002, p. 7645-7657, Vol. 22, No. 21
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.21.7645-7657.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Rac2, a Hematopoiesis-Specific Rho GTPase, Specifically Regulates Mast Cell Protease Gene Expression in Bone Marrow-Derived Mast Cells

Yi Gu,1 Michael C. Byrne,2 Nivanka C. Paranavitana,3 Bruce Aronow,4 Jamie E. Siefring,1 Maria D'Souza,1 Heidi F. Horton,2 Lawrence A. Quilliam,3 and David A. Williams1*

Division of Experimental Hematology,1 Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229,4 Wyeth Research, Cambridge, Massachusetts 02140,2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 462023

Received 4 December 2001/ Returned for modification 1 July 2002/ Accepted 8 August 2002

Rho family GTPases activate intracellular kinase cascades to modulate transcription of multiple genes. Previous studies have examined the roles of the ubiquitously expressed Rho GTPase, Rac1, in regulation of gene expression in cell lines and implicated NF-{kappa}B, serum response factor, and kinase signaling pathways in this regulation. To understand the role of the closely related but hematopoiesis-specific Rho GTPase, Rac2, in regulation of gene transcription, we compared the gene expression profiles between wild-type and Rac2-/- bone marrow-derived mast cells. Our data demonstrate remarkable specificity in the regulation of gene expression by Rac2 versus Rac1. Microarray analysis demonstrated that expression of 38 known genes was significantly altered in Rac2-/- mast cells after cytokine stimulation compared with those in wild-type cells. Of these, the expression of the mouse mast cell protease 7 (MMCP-7) gene in wild-type cells was highly induced at the transcriptional level after stimulation with stem cell factor (SCF). In spite of compensatorily increased expression of Rac1 in Rac2-deficient cells, SCF-induced MMCP-7 transcription did not occur. Surprisingly, the loss of MMCP-7 induction was not due to decreased activation of NF-{kappa}B, a transcription factor postulated to lie downstream of Rac1 and known to play a critical role in hematopoietic cell differentiation and proliferation. However, the activities of c-Jun N-terminal kinases (JNKs) were markedly decreased in Rac2-/- mast cells. Our results suggest that cytokine-stimulated activation of MMCP-7 gene transcription is selectively regulated by a Rac2-dependent JNK signaling pathway in primary mast cells and imply a remarkable specificity in the regulation of transcriptional activity by these two highly related Rho GTPases.

* Corresponding author. Mailing address: Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. Phone: (513) 636-0364. Fax: (513) 636-3768. E-mail: david.williams{at}chmcc.org.

Molecular and Cellular Biology, November 2002, p. 7645-7657, Vol. 22, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.21.7645-7657.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yamada, Y., Sanchez-Aguilera, A., Brandt, E. B., McBride, M., Al-Moamen, N. J. H., Finkelman, F. D., Williams, D. A., Cancelas, J. A., Rothenberg, M. E. (2008). FIP1L1/PDGFR{alpha} synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. Blood 112: 2500-2507 [Abstract] [Full Text]  
  • Samayawardhena, L. A., Kapur, R., Craig, A. W. B. (2007). Involvement of Fyn kinase in Kit and integrin-mediated Rac activation, cytoskeletal reorganization, and chemotaxis of mast cells. Blood 109: 3679-3686 [Abstract] [Full Text]  
  • Tian, Y., Autieri, M. V. (2007). Cytokine expression and AIF-1-mediated activation of Rac2 in vascular smooth muscle cells: a role for Rac2 in VSMC activation. Am. J. Physiol. Cell Physiol. 292: C841-C849 [Abstract] [Full Text]  
  • Filippi, M.-D., Szczur, K., Harris, C. E., Berclaz, P.-Y. (2007). Rho GTPase Rac1 is critical for neutrophil migration into the lung. Blood 109: 1257-1264 [Abstract] [Full Text]  
  • Ghiaur, G., Lee, A., Bailey, J., Cancelas, J. A., Zheng, Y., Williams, D. A. (2006). Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment. Blood 108: 2087-2094 [Abstract] [Full Text]  
  • Kalesnikoff, J., Rios, E. J., Chen, C.-C., Nakae, S., Zabel, B. A., Butcher, E. C., Tsai, M., Tam, S.-Y., Galli, S. J. (2006). RabGEF1 regulates stem cell factor/c-Kit-mediated signaling events and biological responses in mast cells.. Proc. Natl. Acad. Sci. USA 103: 2659-2664 [Abstract] [Full Text]  
  • Wang, L., Yang, L., Filippi, M.-D., Williams, D. A., Zheng, Y. (2006). Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment. Blood 107: 98-105 [Abstract] [Full Text]  
  • Piechulek, T., Rehlen, T., Walliser, C., Vatter, P., Moepps, B., Gierschik, P. (2005). Isozyme-specific Stimulation of Phospholipase C-{gamma}2 by Rac GTPases. J. Biol. Chem. 280: 38923-38931 [Abstract] [Full Text]  
  • Munugalavadla, V., Dore, L. C., Tan, B. L., Hong, L., Vishnu, M., Weiss, M. J., Kapur, R. (2005). Repression of c-Kit and Its Downstream Substrates by GATA-1 Inhibits Cell Proliferation during Erythroid Maturation. Mol. Cell. Biol. 25: 6747-6759 [Abstract] [Full Text]  
  • Corbetta, S., Gualdoni, S., Albertinazzi, C., Paris, S., Croci, L., Consalez, G. G., de Curtis, I. (2005). Generation and Characterization of Rac3 Knockout Mice. Mol. Cell. Biol. 25: 5763-5776 [Abstract] [Full Text]  
  • Carstanjen, D., Yamauchi, A., Koornneef, A., Zang, H., Filippi, M.-D., Harris, C., Towe, J., Atkinson, S., Zheng, Y., Dinauer, M. C., Williams, D. A. (2005). Rac2 Regulates Neutrophil Chemotaxis, Superoxide Production, and Myeloid Colony Formation through Multiple Distinct Effector Pathways. J. Immunol. 174: 4613-4620 [Abstract] [Full Text]  
  • Gu, Y., Jasti, A. C., Jansen, M., Siefring, J. E. (2005). RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation, survival, migration, and engraftment of hematopoietic progenitor cells. Blood 105: 1467-1475 [Abstract] [Full Text]  
  • Tonozuka, Y., Minoshima, Y., Bao, Y. C., Moon, Y., Tsubono, Y., Hatori, T., Nakajima, H., Nosaka, T., Kawashima, T., Kitamura, T. (2004). A GTPase-activating protein binds STAT3 and is required for IL-6-induced STAT3 activation and for differentiation of a leukemic cell line. Blood 104: 3550-3557 [Abstract] [Full Text]  
  • Funaba, M., Ikeda, T., Murakami, M., Ogawa, K., Tsuchida, K., Sugino, H., Abe, M. (2003). Transcriptional Activation of Mouse Mast Cell Protease-7 by Activin and Transforming Growth Factor-{beta} Is Inhibited by Microphthalmia-associated Transcription Factor. J. Biol. Chem. 278: 52032-52041 [Abstract] [Full Text]  
  • Pradip, D., Peng, X., Durden, D. L. (2003). Rac2 Specificity in Macrophage Integrin Signaling: POTENTIAL ROLE FOR Syk KINASE. J. Biol. Chem. 278: 41661-41669 [Abstract] [Full Text]  
  • Gu, Y., Filippi, M.-D., Cancelas, J. A., Siefring, J. E., Williams, E. P., Jasti, A. C., Harris, C. E., Lee, A. W., Prabhakar, R., Atkinson, S. J., Kwiatkowski, D. J., Williams, D. A. (2003). Hematopoietic Cell Regulation by Rac1 and Rac2 Guanosine Triphosphatases. Science 302: 445-449 [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»