PMID- 10206983
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 17
DP  - 1999 Apr 23
TI  - Inhibition of T cell signaling by mitogen-activated protein kinase-targeted
      hematopoietic tyrosine phosphatase (HePTP).
PG  - 11693-700
AB  - Activation of T lymphocytes to produce cytokines is regulated by the
      counterbalance of protein-tyrosine kinases and protein-tyrosine phosphatases,
      many of which have a high degree of substrate specificity because of physical
      association with their targets. Overexpression of hematopoietic protein-tyrosine 
      phosphatase (HePTP) results in suppression of T lymphocyte activation as measured
      by T cell antigen receptor-induced activation of transcription factors binding to
      the 5' promoter of the interleukin-2 gene. Efforts to pinpoint the exact site of 
      action and specificity of HePTP in the signaling cascade revealed that HePTP acts
      directly on the mitogen-activated protein (MAP) kinases Erk1 and 2 and
      consequently reduces the magnitude and duration of their catalytic activation in 
      intact T cells. In contrast, HePTP had no effects on N-terminal c-Jun kinase or
      on events upstream of the MAP kinases. The specificity of HePTP correlated with
      its physical association through its noncatalytic N terminus with Erk and another
      MAP kinase, p38, but not Jnk or other proteins. We propose that HePTP plays a
      negative role in antigen receptor signaling by specifically regulating MAP
      kinases in the cytosol and at early time points of T cell activation before the
      activation-induced expression of nuclear dual-specific MAP kinase phosphatases.
FAU - Saxena, M
AU  - Saxena M
AD  - Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San
      Diego, California 92121, USA.
FAU - Williams, S
AU  - Williams S
FAU - Brockdorff, J
AU  - Brockdorff J
FAU - Gilman, J
AU  - Gilman J
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
GR  - etc.
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
RN  - EC 3.1.3.48 (PTPN7 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
SB  - IM
MH  - Enzyme Activation
MH  - Gene Expression Regulation
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/antagonists & inhibitors/*metabolism
MH  - Protein Tyrosine Phosphatases, Non-Receptor
MH  - *Signal Transduction
MH  - Substrate Specificity
MH  - T-Lymphocytes/*metabolism
MH  - Transcription Factor AP-1/metabolism
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - 10.1074/jbc.274.17.11693 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 23;274(17):11693-700. doi: 10.1074/jbc.274.17.11693.