Janus Kinase 2 is associated with a box 1-like motif and phosphorylates a critical tyrosine residue in the cytoplasmic region of cytotoxic T lymphocyte associated molecule-4

Shunsuke Chikuma, Masaaki Murakami, Kumiko Tanaka, Toshimitsu Uede

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17 Citations (Scopus)

Abstract

It is a consensus that a cytotoxic T lymphocyte associated molecule-4 (CTLA-4) transduces inhibitory signal for T cell activation under physiological condition, indicating that this molecule is an important regulator of T cell homeostasis in vivo. It has been reported that phosphorylation and dephosphorylation of tyrosine residue Y-165 in the cytoplasmic region of CTLA-4 play an important role in its negative signaling and cell surface expression. Some signaling molecules such as Src homology 2 protein tyrosine phosphatase 2 (SHP-2) and the p85 subunit of phosphatidylinositol 3 kinase (P13 kinase) associate with phosphorylated tyrosine residue Y-165, through Src homology 2 (SH2) domains. On the other hand, the adapter complex proteins, AP-2 and AP-50 interact with the same tyrosine residue when unphosphorylated, resulting in clathrin-mediated endocytosis of CTLA-4 molecules. The objective of this study is to identify a tyrosine kinase that can directly bind and phosphorylate the critical tyrosine residue, Y-165 in the cytoplasmic domain of CTLA-4. Here, we demonstrated that 1) Janus Kinase 2 (Jak2) was directly associated with a box 1-like motif in the cytoplasmic tail of CTLA-4 molecule, 2) Jak2 phosphorylated Y-165 residue in the cytoplasmic region of CTLA-4 molecule, and 3) Jak2 was associated with CTLA-4 in HUT 78 T cell lines. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalJournal of Cellular Biochemistry
Volume78
Issue number2
Publication statusPublished - 2000
Externally publishedYes

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Keywords

  • Cytotoxic T lymphocyte associated molecule-4 (CTLA-4)
  • Jak2

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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