A novel intramolecular negative regulation of mouse Jak3 activity by tyrosine 820

Sekine, Yuichi; Kikkawa, Kazuna; Witthuhn, Bruce A.; Kashiwakura, Jun-Ichi; Muromoto, Ryuta; Kitai, Yuichi; Fujimuro, Masahiro; Oritani, Kenji; Matsuda, Tadashi

A novel intramolecular negative regulation of mouse Jak3 activity by tyrosine 820

Sekine, Yuichi; Kikkawa, Kazuna; Witthuhn, Bruce A. et al.

International immunology, 2022, 34(6), 303-312

Permalink : https://hdl.handle.net/2115/88131

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アクセス権	open access
URI	https://hdl.handle.net/2115/88131
タイトル	A novel intramolecular negative regulation of mouse Jak3 activity by tyrosine 820
著者	Sekine, Yuichi ; Kikkawa, Kazuna ; Witthuhn, Bruce A. ; Kashiwakura, Jun-Ichi ; Muromoto, Ryuta ; Kitai, Yuichi ; Fujimuro, Masahiro ; Oritani, Kenji ; Matsuda, Tadashi
e-Rad_Researcher 20396295 著者名 Sekine, Yuichi
著者名 Kikkawa, Kazuna
著者名 Witthuhn, Bruce A.
e-Rad_Researcher 90373290 著者名 Kashiwakura, Jun-Ichi
e-Rad_Researcher 30455597 著者名 Muromoto, Ryuta
e-Rad_Researcher 90756165 著者名 Kitai, Yuichi
著者名 Fujimuro, Masahiro
e-Rad_Researcher 70324762 著者名 Oritani, Kenji
e-Rad_Researcher 20212219 著者名 Matsuda, Tadashi
言語	英語
キーワード	cytokine
	signal transducers activators of transcription 5 (STAT5)
	tyrosine-protein kinase
発行日	2022-02-22
出版者	Oxford University Press
収録物名	International immunology
巻(号)	34(6)
ページ	303-312
抄録	Jak3, a member of the Janus kinase family, is essential for the cytokine receptor common gamma chain (gamma c)-mediated signaling. During activation of Jak3, tyrosine residues are phosphorylated and potentially regulate its kinase activity. We identified a novel tyrosine phosphorylation site within mouse Jak3, Y820, which is conserved in human Jak3, Y824. IL-2-induced tyrosine phosphorylation of Jak3 Y824 in human T cell line HuT78 cells was detected by using a phosphospecific, pY824, antibody. Mutation of mouse Jak3 Y820 to alanine (Y820A) showed increased autophosphorylation of Jak3 and enhanced signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation and transcriptional activation. Stably expressed Jak3 Y820A in F7 cells, an IL-2 responsive mouse pro-B cell line Ba/F3, exhibited enhanced IL-2-dependent cell growth. Mechanistic studies demonstrated that interaction between Jak3 and STAT5 increased in Jak3 Y820A compared to wild-type Jak3.These data suggest that Jak3 Y820 plays a role in negative regulation of Jak3mediated STAT5 signaling cascade upon IL-2-stimulation. We speculate that this occurs through an interaction promoted by the tyrosine phosphorylated Y820 or a conformational change by Y820 mutation with either the STAT directly or with the recruitment of molecules such as phosphatases via a SH2 interaction. Additional studies will focus on these interactions as Jak3 plays a crucial role in disease and health.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This is a pre-copyedited, author-produced version of an article accepted for publication in International Immunology following peer review. The version of record "International Immunology Volume 34, Issue 6, June 2022, Pages 303–312" is available online at: https://doi.org/10.1093/intimm/dxac005.
PISSN	0953-8178
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1093/intimm/dxac005