Premium
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
Author(s) -
Chikuma Shunsuke,
Murakami Masaaki,
Tanaka Kumiko,
Uede Toshimitsu
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(20000801)78:2<241::aid-jcb7>3.0.co;2-k
Subject(s) - protein tyrosine phosphatase , sh2 domain , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , immunoreceptor tyrosine based activation motif , tyrosine , biology , tyrosine kinase , tyrosine phosphorylation , phosphorylation , biochemistry , chemistry , signal transduction
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 (PI3 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. J. Cell. Biochem. 78:241–250, 2000. © 2000 Wiley‐Liss, Inc.