Publication Date:
1999-04-24
Description:
T cell receptor (TCR) signaling requires activation of Zap-70 and Src family tyrosine kinases, but requirements for other tyrosine kinases are less clear. Combined deletion in mice of two Tec kinases, Rlk and Itk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitro and adaptive immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in rlk-/-itk-/- cells, but intermediate events including inositol trisphosphate production, calcium mobilization, and mitogen-activated protein kinase activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-gamma activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schaeffer, E M -- Debnath, J -- Yap, G -- McVicar, D -- Liao, X C -- Littman, D R -- Sher, A -- Varmus, H E -- Lenardo, M J -- Schwartzberg, P L -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):638-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Human Genome Research Institute, National Cancer Institute, National Institute for Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10213685" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoptosis
;
CD4-CD8 Ratio
;
Calcium Signaling
;
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
;
Diglycerides/metabolism
;
Gene Targeting
;
Inositol Phosphates/metabolism
;
Interferon-gamma/biosynthesis
;
Interleukin-2/biosynthesis/pharmacology
;
Isoenzymes/metabolism
;
Killer Cells, Natural/immunology
;
Lymphocyte Activation
;
Mice
;
Mutation
;
Phospholipase C gamma
;
Phosphorylation
;
Protein-Tyrosine Kinases/genetics/*metabolism
;
Receptors, Antigen, T-Cell/*metabolism
;
*Signal Transduction
;
T-Lymphocytes/*enzymology/*immunology
;
Toxoplasmosis, Animal/immunology
;
Type C Phospholipases/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
