Abstract

The project described in this application will focus the mechanisms by which ligation of the T-cell antigen receptor (TcR) and IL-2 receptor activate Ras GTPases in T cells. The downstream consequences of Ras activation, particularly IL-2 promoter activation, will also be investigated.
The specific aims of this application are: (1) to examine the roles of Shc, Grb2, and Crk adaptor proteins in receptor-mediated Ras activation, (2) to define the contributions of PKC-epsilon and phosphatidylcholine-specific phospholipase C (PC-PLC) to the activation of the Raf kinase in T cells, and (3) to determine whether Ras activation is involved in the downstream stimulation of JNKs by TcR and co-stimulatory signals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070758-02
Application #
2390929
Study Section
Experimental Immunology Study Section (EI)
Project Start
1996-06-04
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Alzabin, Saba; Pyarajan, Saiju; Yee, Herman et al. (2010) Hematopoietic progenitor kinase 1 is a critical component of prostaglandin E2-mediated suppression of the anti-tumor immune response. Cancer Immunol Immunother 59:419-29
Sawasdikosol, Sansana; Russo, Kristin M; Burakoff, Steven J (2003) Hematopoietic progenitor kinase 1 (HPK1) negatively regulates prostaglandin E2-induced fos gene transcription. Blood 101:3687-9
Fragoso, Roben; Ren, Dejian; Zhang, Xiaoping et al. (2003) Lipid raft distribution of CD4 depends on its palmitoylation and association with Lck, and evidence for CD4-induced lipid raft aggregation as an additional mechanism to enhance CD3 signaling. J Immunol 170:913-21
Baksh, Shairaz; Widlund, Hans R; Frazer-Abel, Ashley A et al. (2002) NFATc2-mediated repression of cyclin-dependent kinase 4 expression. Mol Cell 10:1071-81
Tkaczuk, Jean; Yu, Chao-Lan; Baksh, Shairaz et al. (2002) Effect of anti-IL-2Ralpha antibody on IL-2-induced Jak/STAT signaling. Am J Transplant 2:31-40
Yu, C L; Jin, Y J; Burakoff, S J (2000) Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation. J Biol Chem 275:599-604
Pratt, J C; van den Brink, M R; Igras, V E et al. (1999) Requirement for Shc in TCR-mediated activation of a T cell hybridoma. J Immunol 163:2586-91
Pratt, J C; Sawasdikosol, S; van den Brink, M R et al. (1999) Positive and negative signaling pathways. Transplant Proc 31:772-4
Tang, J; Sawasdikosol, S; Chang, J H et al. (1999) SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling. Proc Natl Acad Sci U S A 96:9775-80
Jin, Y J; Yu, C L; Burakoff, S J (1999) Human 70-kDa SHP-1L differs from 68-kDa SHP-1 in its C-terminal structure and catalytic activity. J Biol Chem 274:28301-7

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