A role for SHPS-1/SIRPα1 in IL-1β- and TNFα-dependent signaling

Authors

Arm R. Amin, Marshall UniversityFollow
Kazuya Machida
Kumi Oshima
Myat Lin Oa
Aye Aye Thant
Takeshi Senga
Satoru Matsuda
Anwarul Azim Akhand
Akito Maeda
Tomohiro Kurosaki
Michinari Hamaguchi

Document Type

Article

Publication Date

12-2002

Abstract

We investigated the role of SHPS-1/SIRPα1 in IL-1β and TNFα-dependent signaling that leads to the activation of Erk 1/2 and Akt. Treatment of Balb3T3 cells with IL-1β or TNFα activated tyrosine phosphorylation of SHPS-1, its association with SHP-2 and the phosphorylation of Erk 1/2 and Akt. PP1, a specific inhibitor for the Src family protein tyrosine kinases, strongly inhibited tyrosine phosphorylation of SHPS-1 and complex formation of SHPS-1 with SHP-2 by IL1β. In addition, PP1 substantially inhibited the IL-2β and TNFα-dependent activation of Erk 1/2 and Akt. Exogenous expression of either SHPS-1 mutants that lack SHP-2 binding function or a dominant negative mutant of SHP-2 markedly inhibited the activation of Erk 1/2 and Akt by IL-1β, whereas wild type SHPS-1 did not. Moreover, IL-1β-stimulation induced association of SHPS-1 with IL-1RAcP, a second subunit of IL-1 receptor, whereas expression of SHPS-1 mutant that lack SHP-2 binding function clearly blocked the association and tyrosine phosphorylation of endogenous SHPS-1. Taken together, our results strongly suggest that activation of Erk 1/2 and Akt by proinflammatory cytokines requires tyrosine phosphorylation of SHPS-1 and subsequent association of SHPS-1 with SHP-2.

Comments

Copyright © 2002 Nature Publishing Group All rights reserved.

Recommended Citation

Ruhul Amin, A., Machida, K., Oshima, K. et al. A role for SHPS-1/SIRPα1 in IL-1β- and TNFα-dependent signaling. Oncogene 21, 8871–8878 (2002). https://doi.org/10.1038/sj.onc.1206018