PMID- 10601992
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20180423
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 29
IP  - 12
DP  - 1999 Dec
TI  - Characterization of TCR-induced receptor-proximal signaling events negatively
      regulated by the protein tyrosine phosphatase PEP.
PG  - 3845-54
AB  - The proline-, glutamic acid-, serine- and threonine-enriched protein tyrosine
      phosphatase PEP, which is expressed primarily in hematopoietic cells, was
      recently discovered to be physically associated with the 50-kDa cytosolic protein
      tyrosine kinase (PTK) Csk, an important suppressor of Src family PTK, including
      Lck and Fyn in T cells. We report that this phosphatase has an inhibitory effect 
      on TCR-induced transcriptional activation of the c-fos proto-oncogene and
      elements from the IL-2 gene promoter. Catalytically inactive mutants of PEP had
      no effects in these assays. Expression of PEP also reduced activation of the
      N-terminal c-Jun kinase Jnk2 in response to receptor ligation, but not in
      response to UV light. In agreement with a more receptor-proximal site of action, 
      we found that PEP reduced the TCR-induced increase in tyrosine phosphorylation of
      an Lck mutant, Lck-Y505F, which is only phosphorylated on tyrosine 394, the
      positive regulatory site. Finally, we observed that PEP reduced c-fos activation 
      in a synergistic manner with Csk, supporting the notion that these two enzymes
      form a functional team acting on Src family kinases involved in TCR signaling.
FAU - Gjorloff-Wingren, A
AU  - Gjorloff-Wingren A
AD  - Laboratory of Signal Transduction, Sidney Kimmel Cancer Center, San Diego, USA.
FAU - Saxena, M
AU  - Saxena M
FAU - Williams, S
AU  - Williams S
FAU - Hammi, D
AU  - Hammi D
FAU - Mustelin, T
AU  - Mustelin T
LA  - eng
GR  - AI35603/AI/NIAID NIH HHS/United States
GR  - AI41481/AI/NIAID NIH HHS/United States
GR  - GM48960/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 3.1.3.48 (PTPN12 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 12)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphocyte Activation/immunology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 12
MH  - Protein Tyrosine Phosphatases/*immunology
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - Signal Transduction/*immunology
MH  - T-Lymphocytes/*immunology
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1002/(SICI)1521-4141(199912)29:12<3845::AID-IMMU3845>3.0.CO;2-U [doi]
PST - ppublish
SO  - Eur J Immunol. 1999 Dec;29(12):3845-54. doi:
      10.1002/(SICI)1521-4141(199912)29:12<3845::AID-IMMU3845>3.0.CO;2-U.