PMID- 10415025
OWN - NLM
STAT- MEDLINE
DCOM- 19990812
LR  - 20161124
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 3
DP  - 1999 Aug 1
TI  - Direct suppression of TCR-mediated activation of extracellular signal-regulated
      kinase by leukocyte protein tyrosine phosphatase, a tyrosine-specific
      phosphatase.
PG  - 1282-8
AB  - Leukocyte protein tyrosine phosphatase (LC-PTP)/hemopoietic PTP is a human
      cytoplasmic PTP that is predominantly expressed in the hemopoietic cells.
      Recently, it was reported that hemopoietic PTP inhibited TCR-mediated signal
      transduction. However, the precise mechanism of the inhibition was not
      identified. Here we report that extracellular signal-regulated kinase (ERK) is
      the direct target of LC-PTP. LC-PTP dephosphorylated ERK2 in vitro. Expression of
      wild-type LC-PTP in 293T cells suppressed the phosphorylation of ERK2 by a mutant
      MEK1, which was constitutively active regardless of upstream activation signals. 
      No suppression of the phosphorylation was observed by LC-PTPCS, a catalytically
      inactive mutant. In Jurkat cells, LC-PTP suppressed the ERK and p38
      mitogen-activated protein kinase cascades. LC-PTP and LC-PTPCS made complexes
      with ERK1, ERK2, and p38alpha, but not with the gain-of-function sevenmaker ERK2 
      mutant (D321N). A small deletion (aa 1-46) in the N-terminal portion of LC-PTP or
      Arg to Ala substitutions at aa 41 and 42 resulted in the loss of ERK binding
      activity. These LC-PTP mutants revealed little inhibition of the ERK cascade
      activated by TCR cross-linking. On the other hand, the wild-type LC-PTP did not
      suppress the phosphorylation of sevenmaker ERK2 mutant. Thus, the complex
      formation of LC-PTP with ERK is the essential mechanism for the suppression.
      Taken collectively, these results indicate that LC-PTP suppresses
      mitogen-activated protein kinase directly in vivo.
FAU - Oh-hora, M
AU  - Oh-hora M
AD  - Biomedical Research Center, Osaka University Medical School, Japan.
FAU - Ogata, M
AU  - Ogata M
FAU - Mori, Y
AU  - Mori Y
FAU - Adachi, M
AU  - Adachi M
FAU - Imai, K
AU  - Imai K
FAU - Kosugi, A
AU  - Kosugi A
FAU - Hamaoka, T
AU  - Hamaoka T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
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  - AIM
SB  - IM
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists &
      inhibitors/*metabolism
MH  - Cell Line
MH  - Enzyme Activation/immunology
MH  - Genetic Vectors/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Jurkat Cells
MH  - Kidney
MH  - MAP Kinase Kinase 1
MH  - Macromolecular Substances
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - *Mitogen-Activated Protein Kinases
MH  - Phosphorylation
MH  - Protein Binding/immunology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/genetics/*physiology
MH  - Protein Tyrosine Phosphatases, Non-Receptor
MH  - Protein-Serine-Threonine Kinases/genetics/metabolism
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Receptors, Antigen, T-Cell/*physiology
MH  - Recombinant Fusion Proteins/biosynthesis/metabolism
MH  - Transfection
MH  - Tyrosine/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/07/22 00:00
MHDA- 1999/07/22 00:01
CRDT- 1999/07/22 00:00
PHST- 1999/07/22 00:00 [pubmed]
PHST- 1999/07/22 00:01 [medline]
PHST- 1999/07/22 00:00 [entrez]
AID - ji_v163n3p1282 [pii]
PST - ppublish
SO  - J Immunol. 1999 Aug 1;163(3):1282-8.