Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.
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.
Schaeffer
E M
EM
National Human Genome Research Institute, National Cancer Institute, National Institute for Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Debnath
J
J
Yap
G
G
McVicar
D
D
Liao
X C
XC
Littman
D R
DR
Sher
A
A
Varmus
H E
HE
Lenardo
M J
MJ
Schwartzberg
P L
PL
D000818:Animals; D017209:Apoptosis; D016516:CD4-CD8 Ratio; D020013:Calcium Signaling; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D018390:Gene Targeting; D007295:Inositol Phosphates / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D009154:Mutation; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology; D010738:Type C Phospholipases / Q000378:metabolism
D004075:Diglycerides; D007295:Inositol Phosphates; D007376:Interleukin-2; D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma