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Lck regulates the threshold of activation in primary T cells, while both Lck and Fyn contribute to the magnitude of the extracellular signal-related kinase response.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2006 Nov; Vol. 26 (22), pp. 8655-65. Date of Electronic Publication: 2006 Sep 11. - Publication Year :
- 2006
-
Abstract
- The src family kinases p56lck (Lck) and p59fyn (Fyn) are the most proximal signaling molecules to be activated downstream of the T-cell receptor. Using an inducible transgenic model, we can regulate the expression of Lck in primary T cells and ask how the signaling cascade and differentiation potential are affected by the absence or the presence of reduced levels of Lck. We show that in naïve T cells, Lck controls the threshold of activation by preferentially regulating multiple signaling pathways that result in the mobilization of Ca2+ through activation of phospholipase C-gamma and protein kinase C as well as activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway. Fyn is also able to stimulate the ERK/MAPK pathway in primary T cells but has little influence on the mobilization of Ca2+. Only Lck efficiently stimulates production of diacylglycerol and therefore RasGRP1 recruitment to the plasma membrane and phosphorylation of Shc, suggesting that Fyn activates ERK via a different upstream signaling route. Finally, we show that signals through Lck are essential for the development of T-cell-effector potential, particularly for effective cytokine transcription.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Animals
CD4-Positive T-Lymphocytes metabolism
Calcium Signaling
Cell Proliferation
Cytokines biosynthesis
Extracellular Signal-Regulated MAP Kinases metabolism
Gene Expression Regulation
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) genetics
Membrane Proteins metabolism
Mice
Phospholipase C gamma metabolism
Phosphorylation
Up-Regulation
ZAP-70 Protein-Tyrosine Kinase metabolism
Lymphocyte Activation
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) physiology
MAP Kinase Signaling System
Proto-Oncogene Proteins c-fyn physiology
Receptors, Antigen, T-Cell metabolism
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 26
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16966372
- Full Text :
- https://doi.org/10.1128/MCB.00168-06