Activation of the B cell antigen receptor (BCR) requires the efficient activation of the Syk protein tyrosine kinase (PTK). B cells deficient are unable to generate second messengers following receptor engagement. Moreover, mice deficient in syk are unable to develop normal numbers of mature B cells. Hence, the Syk PTK plays a requisite role in the signaling cascade of the BCR. While much has been learned about the Syk PTK, there is still little appreciation or insight into how this kinase regulates B cell activation. In this project (Project 1), we will analyze a novel regulatory mechanism for regulating Syk activity. In addition, we will analyze the dynamics of Syk function using a real time approach combined with a molecular dissection of the signaling parameters which regulate cytoskeletal alterations in B cell morphology following receptor activation. Together, these studies will likely provide novel insights into how Syk regulates B cell activation and also insights into how Syk may regulate receptors expression on other immune cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI047330-03
Application #
6652713
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2002-09-01
Project End
2003-07-31
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
$241,412
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Bui, Jack D; Carayannopoulos, Leonidas N; Lanier, Lewis L et al. (2006) IFN-dependent down-regulation of the NKG2D ligand H60 on tumors. J Immunol 176:905-13