Abstract

The purpose of this project is to study signal transduction and cell cycle progression using neurofibromin-deficient B lymphocytes generated by transferring Nf1-/-fetal liver cells into Rag1-/- mice. The identity of a specific 75-78kD protein, which comigrates with Btk, and which is specifically not phosphorylated on tyrosine residues in antigen receptor- stimulated neurofibromin-deficient B-cells will be determined. The ability of these cells to proliferate in response to antigen receptor crosslinking, CD40 ligation, and IL-4 will be examined. Reconstituted mice will be observed long-term for lymphoproliferation and responses to T- dependent and T-independent antigens will also be examined. Studies will be performed to examine whether neurofibromin plays a role in promoting specific tyrosine phosphorylation events, or whether it is a negative regulator of specific phosphotyrosyl phosphatases. Proteins that specifically associate with neurofibromin in B lymphocytes will be purified.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA069618-03
Application #
2769837
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Finerty, John F
Project Start
1996-09-01
Project End
1999-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Cariappa, Annaiah; Pillai, Shiv (2002) Antigen-dependent B-cell development. Curr Opin Immunol 14:241-9
Kim, Tae Jin; Cariappa, Annaiah; Iacomini, John et al. (2002) Defective proliferative responses in B lymphocytes and thymocytes that lack neurofibromin. Mol Immunol 38:701-8
Cariappa, A; Tang, M; Parng, C et al. (2001) The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21. Immunity 14:603-15
Chen, L; Haider, K; Ponda, M et al. (2001) Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase. J Biol Chem 276:21737-44
Cariappa, A; Liou, H C; Horwitz, B H et al. (2000) Nuclear factor kappa B is required for the development of marginal zone B lymphocytes. J Exp Med 192:1175-82
Ho, S C; Chaudhuri, S; Bachhawat, A et al. (2000) Accelerated proteasomal degradation of membrane Ig heavy chains. J Immunol 164:4713-9
Cariappa, A; Kim, T J; Pillai, S (1999) Accelerated emigration of B lymphocytes in the Xid mouse. J Immunol 162:4417-23
Ho, S C; Rajagopalan, S; Chaudhuri, S et al. (1999) Membrane anchoring of calnexin facilitates its interaction with its targets. Mol Immunol 36:1-12
Novina, C D; Kumar, S; Bajpai, U et al. (1999) Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase. Mol Cell Biol 19:5014-24
Chen, L; Kim, T J; Pillai, S (1998) Inhibition of caspase activity prevents anti-IgM induced apoptosis but not ceramide generation in WEHI 231 B cells. Mol Immunol 35:195-205