PMID- 10652356
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 5
DP  - 2000 Feb 4
TI  - Regulation of protein kinase Ctheta function during T cell activation by
      Lck-mediated tyrosine phosphorylation.
PG  - 3603-9
AB  - Protein kinase C theta (PKCtheta) is a novel Ca(2+)-independent PKC isoform,
      which is selectively expressed in skeletal muscle and hematopoietic cells,
      especially T cells. In T cells, it colocalizes with the T cell antigen receptor
      (TCR).CD3 complex in antigen-stimulated T cells and is involved in the
      transcriptional activation of the interleukin-2 gene. In the present study, we
      report that PKCtheta is tyrosine phosphorylated in Jurkat T cells upon TCR.CD3
      activation. The Src family protein-tyrosine kinase, Lck, was critical in
      TCR-induced tyrosine phosphorylation of PKCtheta. Lck phosphorylated and was
      associated with the regulatory domain of PKCtheta both in vitro and in intact
      cells. This association was constitutive, but it was enhanced by T cell
      activation, with both Src-homology 2 and Src-homology 3 domains of Lck
      contributing to it. Tyrosine 90 (Tyr-90) in the regulatory domain of PKCtheta was
      identified as the major phosphorylation site by Lck. A constitutively active
      mutant of PKCtheta (A148E) could enhance proliferation of Jurkat T cells and
      synergized with ionomycin to induce nuclear factor of T cells activity. However, 
      mutation of Tyr-90 into phenylalanine markedly reduced (or abolished) these
      activities. These results suggest that Lck plays an important role in tyrosine
      phosphorylation of PKCtheta, which may in turn modulate the physiological
      functions of PKCtheta during TCR-induced T cell activation.
FAU - Liu, Y
AU  - Liu Y
AD  - Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San
      Diego, California 92121, USA.
FAU - Witte, S
AU  - Witte S
FAU - Liu, Y C
AU  - Liu YC
FAU - Doyle, M
AU  - Doyle M
FAU - Elly, C
AU  - Elly C
FAU - Altman, A
AU  - Altman A
LA  - eng
GR  - AI09881/AI/NIAID NIH HHS/United States
GR  - CA35299/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Isoenzymes)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
RN  - EC 2.7.11.13 (PRKCQ protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-theta)
SB  - IM
MH  - Humans
MH  - Isoenzymes/*metabolism
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - Protein Kinase C-theta
MH  - *Signal Transduction
MH  - T-Lymphocytes/*metabolism
MH  - Tyrosine
EDAT- 2000/02/01 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1074/jbc.275.5.3603 [doi]
AID - S0021-9258(18)30945-1 [pii]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 4;275(5):3603-9. doi: 10.1074/jbc.275.5.3603.