Jennifer N. Wu
University of Pennsylvania
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Publication
Featured researches published by Jennifer N. Wu.
Immunity | 2003
Sally A. Newbrough; Attila Mócsai; Regina A. Clemens; Jennifer N. Wu; Michael Silverman; Andrew L. Singer; Clifford A. Lowell; Gary A. Koretzky
Abstract While the contribution of intracellular adaptor proteins to lymphocyte activation has been well studied, the function of these molecules in innate immune effector cells such as neutrophils has not been extensively addressed. Here we demonstrate a critical role for the adaptor molecule SH2 domain-containing leukoctye-specific phosphoprotein of 76 kDa (SLP-76) in FcγR and integrin signaling. Stimulation of these receptors induces tyrosine phosphorylation and cytoplasmic relocalization of SLP-76 in freshly isolated murine neutrophils. Neutrophils lacking SLP-76 demonstrate decreased FcγR-induced calcium flux and reactive oxygen intermediate (ROI) production in response to immune complex stimulation. More dramatically, SLP-76 −/− neutrophils fail to produce ROI, spread, or activate critical downstream regulators in response to integrin ligation. These results provide genetic evidence for a critical role of SLP-76 in the regulation of neutrophil function.
Journal of Immunology | 2004
Jennifer N. Wu; Martha S. Jordan; Michael Silverman; Erik J. Peterson; Gary A. Koretzky
The adapter molecule Src homology 2 (SH2) domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is essential for FcεRI-mediated signaling, degranulation and IL-6 production in mast cells. To test the structural requirements of SLP-76 in mast cell signaling and function, we have studied the functional responses of murine bone marrow-derived mast cells (BMMCs) expressing mutant forms of SLP-76. We found that the N-terminal tyrosines as well as the central proline-rich region of SLP-76 are required for participation of SLP-76 in FcεRI-mediated signaling and function. The C-terminal SH2 domain of SLP-76 also contributes to optimal function of SLP-76 in mast cells. Another adapter molecule, adhesion- and degranulation-promoting adapter protein (ADAP), is known to bind the SH2 domain of SLP-76, and cell line studies have implicated ADAP in mast cell adhesion and FcεRI-induced degranulation. Surprisingly, we found that mast cells lacking ADAP expression demonstrate no defects in FcεRI-induced adhesion, granule release, or IL-6 production, and that ADAP-deficient mice produce a normal passive systemic anaphylactic response. Thus, failure to bind ADAP does not underlie the functional defects exhibited by SLP-76 SH2 domain mutant-expressing mast cells.
Journal of Immunology | 2006
Jennifer N. Wu; Shereen Gheith; Natalie A. Bezman; Qing-Hua Liu; Lindsey V. Fostel; Andrew M. Swanson; Bruce D. Freedman; Gary A. Koretzky; Erik J. Peterson
Adhesion- and degranulation-promoting adapter protein (ADAP) is required in TCR-induced activation and proliferation of peripheral T cells. Loss of ADAP also impairs TCR-initiated inside-out activation of the integrin LFA-1 (CD11a/CD18, αLβ2). In this study, we demonstrate that ADAP-deficient CD4/CD8 double-positive (DP) cells have a diminished ability to proliferate, and that these DP thymocytes up-regulate CD69 poorly in vivo. Moreover, in both MHC class I- and class II-restricted TCR transgenic models, loss of ADAP interferes with both positive and negative selection. ADAP deficiency also impairs the ability of transgene-bearing DP thymocytes to form conjugates with Ag-loaded presenting cells. These findings suggest that ADAP is critical for thymocyte development and selection.
Immunologic Research | 2003
Gary A. Koretzky; Farhad Abtahian; Geo Derimanov; Sally A. Dmowski; Anastasia Guerriero; Martha S. Jordan; Jonathan S. Maltzman; Benjamin A. Olenchock; Andrew L. Singer; Jennifer N. Wu; Xiao-Ping Zhong
Adapter proteins, molecules with modular domains that mediate intermolecular interactions, play critical roles in the regulation of signaling events in all cell types. A major focus of our laboratory has been to examine the role of adapter molecules in hematopoietic cell development and activation. This review will describe the approaches we are taking to identify such proteins and to determine the mechanisms by which they exert their functions. This work represents the enormous efforts of the students and postdocs who have committed themselves to these projects, as well as the important collaborations we have developed with other investigators at the University of Pennsylvania and elsewhere.
Journal of Cell Biology | 2006
Benjamin A. Olenchock; Rishu Guo; Michael Silverman; Jennifer N. Wu; Jeffery H. Carpenter; Gary A. Koretzky; Xiao-Ping Zhong
Olenchock et al. 2006. J. Exp. Med. doi:10.1084/jem.20052424[OpenUrl][1][Abstract/FREE Full Text][2] [1]: {openurl}?query=rft.jtitle%253DJ.%2BExp.%2BMed.%26rft_id%253Dinfo%253Adoi%252F10.1084%252Fjem.20052424%26rft_id%253Dinfo%253Apmid%252F16717114%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%
Science | 2001
Erik J. Peterson; Melody L. Woods; Sally A. Dmowski; Geo Derimanov; Martha S. Jordan; Jennifer N. Wu; Peggy S. Myung; Qing-Hua Liu; Jonathan T. Pribila; Bruce D. Freedman; Yoji Shimizu; Gary A. Koretzky
Blood | 2007
Jun-ichiro Suzuki; Sho Yamasaki; Jennifer N. Wu; Gary A. Koretzky; Takashi Saito
Seminars in Immunology | 2004
Jennifer N. Wu; Gary A. Koretzky
Journal of Biological Chemistry | 2004
Andrew L. Singer; Stephen C. Bunnell; Amrom E. Obstfeld; Martha S. Jordan; Jennifer N. Wu; Peggy Myung; Lawrence E. Samelson; Gary A. Koretzky
Blood | 2009
Phoebe E. Harvey; Mary Lynn Nierodzik; Jennifer N. Wu