Direct suppression of TCR-mediated activation of extracellular signal- regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine- specific phosphatase

Masatsugu Oh-Hora, Masato Ogata, Yoshiko Mori, Masaaki Adachi, Kohzoh Imai, Atsushi Kosugi, Toshiyuki Hamaoka

Research output: Contribution to journalArticle

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Abstract

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 p38α, 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 aa41 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.

Original languageEnglish
Pages (from-to)1282-1288
Number of pages7
JournalJournal of Immunology
Volume163
Issue number3
Publication statusPublished - Aug 1 1999
Externally publishedYes

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Protein Tyrosine Phosphatases
Extracellular Signal-Regulated MAP Kinases
Phosphoric Monoester Hydrolases
Tyrosine
Leukocytes
Phosphorylation
Jurkat Cells
HEK293 Cells
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Signal Transduction

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Direct suppression of TCR-mediated activation of extracellular signal- regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine- specific phosphatase. / Oh-Hora, Masatsugu; Ogata, Masato; Mori, Yoshiko; Adachi, Masaaki; Imai, Kohzoh; Kosugi, Atsushi; Hamaoka, Toshiyuki.

In: Journal of Immunology, Vol. 163, No. 3, 01.08.1999, p. 1282-1288.

Research output: Contribution to journalArticle

Oh-Hora, Masatsugu ; Ogata, Masato ; Mori, Yoshiko ; Adachi, Masaaki ; Imai, Kohzoh ; Kosugi, Atsushi ; Hamaoka, Toshiyuki. / Direct suppression of TCR-mediated activation of extracellular signal- regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine- specific phosphatase. In: Journal of Immunology. 1999 ; Vol. 163, No. 3. pp. 1282-1288.
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