PMID- 10213685
OWN - NLM
STAT- MEDLINE
DCOM- 19990511
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 284
IP  - 5414
DP  - 1999 Apr 23
TI  - Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and
      immunity.
PG  - 638-41
AB  - 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.
FAU - Schaeffer, E M
AU  - Schaeffer EM
AD  - National Human Genome Research Institute, National Cancer Institute, National
      Institute for Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
FAU - Debnath, J
AU  - Debnath J
FAU - Yap, G
AU  - Yap G
FAU - McVicar, D
AU  - McVicar D
FAU - Liao, X C
AU  - Liao XC
FAU - Littman, D R
AU  - Littman DR
FAU - Sher, A
AU  - Sher A
FAU - Varmus, H E
AU  - Varmus HE
FAU - Lenardo, M J
AU  - Lenardo MJ
FAU - Schwartzberg, P L
AU  - Schwartzberg PL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Diglycerides)
RN  - 0 (Inositol Phosphates)
RN  - 0 (Interleukin-2)
RN  - 0 (Isoenzymes)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.- (Tec protein-tyrosine kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (emt protein-tyrosine kinase)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - CD4-CD8 Ratio
MH  - Calcium Signaling
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Diglycerides/metabolism
MH  - Gene Targeting
MH  - Inositol Phosphates/metabolism
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-2/biosynthesis/pharmacology
MH  - Isoenzymes/metabolism
MH  - Killer Cells, Natural/immunology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mutation
MH  - Phospholipase C gamma
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - *Signal Transduction
MH  - T-Lymphocytes/*enzymology/*immunology
MH  - Toxoplasmosis, Animal/immunology
MH  - Type C Phospholipases/metabolism
EDAT- 1999/04/24 00:00
MHDA- 1999/04/24 00:01
CRDT- 1999/04/24 00:00
PHST- 1999/04/24 00:00 [pubmed]
PHST- 1999/04/24 00:01 [medline]
PHST- 1999/04/24 00:00 [entrez]
AID - 10.1126/science.284.5414.638 [doi]
PST - ppublish
SO  - Science. 1999 Apr 23;284(5414):638-41. doi: 10.1126/science.284.5414.638.