Hui Zhang

Publications (2)9.79 Total impact

• Article: Human neutrophils coordinate chemotaxis by differential activation of Rac1 and Rac2.

  Hui Zhang, Chunxiang Sun, Michael Glogauer, Gary M Bokoch
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  ABSTRACT: Rac1 and Rac2, members of the small Rho GTPase family, play essential roles in coordinating directional migration and superoxide production during neutrophil responses to chemoattractants. Although earlier studies in Rac1 and Rac2 knockout mice have demonstrated unique roles for each Rac isoform in chemotaxis and NADPH oxidase activation, it is still unclear how human neutrophils use Rac1 and Rac2 to achieve their immunological responses to foreign agent stimulation. In the current study, we used TAT dominant-negative Rac1-T17N and Rac2-T17N fusion proteins to acutely alter the activity of Rac1 and Rac2 individually in human neutrophils. We demonstrate distinct activation kinetics and different roles for Rac1 and Rac2 in response to low vs high concentrations of fMLP. These observations were verified using neutrophils from mice in which Rac1 or Rac2 was genetically absent. Based on these results, we propose a model to explain how human neutrophils kill invading microbes while limiting oxidative damage to the adjacent surrounding healthy tissue through the differential activation of Rac1 and Rac2 in response to different concentrations of chemoattractant.
  The Journal of Immunology 09/2009; 183(4):2718-28. · 5.79 Impact Factor
• Article: Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1.

  Jill E Chrencik, Alexei Brooun, Hui Zhang, Irimpan I Mathews, Greg L Hura, Scott A Foster, J Jefferson P Perry, Markus Streiff, Paul Ramage, Hans Widmer, Gary M Bokoch, John A Tainer, Gisbert Weckbecker, Peter Kuhn
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  ABSTRACT: The guanine nucleotide exchange factor (GEF) Vav1 plays an important role in T-cell activation and tumorigenesis. In the GEF superfamily, Vav1 has the ability to interact with multiple families of Rho GTPases. The structure of the Vav1 DH-PH-CRD/Rac1 complex to 2.6 A resolution reveals a unique intramolecular network of contacts between the Vav1 cysteine-rich domain (CRD) and the C-terminal helix of the Vav1 Dbl homology (DH) domain. These unique interactions stabilize the Vav1 DH domain for its intimate association with the Switch II region of Rac1 that is critical for the displacement of the guanine nucleotide. Small angle x-ray scattering (SAXS) studies support this domain arrangement for the complex in solution. Further, mutational analyses confirms that the atypical CRD is critical for maintaining both optimal guanine nucleotide exchange activity and broader specificity of Vav family GEFs. Taken together, the data outline the detailed nature of Vav1's ability to contact a range of Rho GTPases using a novel protein-protein interaction network.
  Journal of Molecular Biology 08/2008; 380(5):828-43. · 4.00 Impact Factor