Novel functional interaction between Na/H exchanger 1 and tyrosine phosphatase SHP-2

Comp Physiol 292: R2406–R2416, 2007. First published February 8, 2007; doi:10.1152/ajpregu.00859.2006.—Besides being a intracellu-lar pH (pHi) regulator, Na/H exchanger (NHE)1 has recently been postulated as a membrane scaffold that assembles protein complexes and coordinates various signaling pathways. The aim of the present study was to uncover NHE1 interactive partners and study their functional implications. NHE1 interactive partners were screened in the mouse brain with a signal transduction AntibodyArray. Ten of 400 tested proteins appeared to be potentially associated with NHE1. These partners have been shown to be involved in either cell prolif-erative or apoptotic pathways. The interactions between NHE1 and Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2), Bin1, and heat shock protein (HSP)70 were reciprocally confirmed by coimmunoprecipitation. Moreover, in vitro binding data have shown that NHE1 COOH terminus interacts directly with SHP-2