HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A corrigendum has been published All Versions of this Article: 292/6/R2406    most recent 00859.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Xue, J. Articles by Haddad, G. G. Search for Related Content PubMed PubMed Citation Articles by Xue, J. Articles by Haddad, G. G.

WATER AND ELECTROLYTE HOMEOSTASIS

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

Departments of ¹Pediatrics and ²Neuroscience, University of California San Diego and ³The Rady Children's Hospital, San Diego, California; and Departments of ⁴Medicine, ⁵Pediatrics, and ⁶Human Genetics, Mount Sinai School of Medicine, New York, New York

Submitted 8 December 2006 ; accepted in final form 5 February 2007

Besides being a intracellular pH (pH_i) 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 proliferative 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. The functional significance of the association between NHE1 and SHP-2 was further investigated by measuring pH_i, cell proliferation, and cell death with the fluorescent dye BCECF, [³H]thymidine incorporation, and medium lactate dehydrogenase activity, respectively. Our results revealed that cells with SHP-2 overexpression exhibited a higher steady-state pH_i and a faster, NHE1-dependent pH_i recovery rate from acid load in HEPES buffer. In addition, SHP-2 overexpression diminished the HOE-642-induced inhibition of cell proliferation and protected cells from hypoxic injury, especially in the presence of HOE-642. Together, our findings demonstrate that SHP-2 not only is physically associated with NHE1 but also modulates NHE1 functions such as pH_i regulation, cell proliferation, and cell death under hypoxia.

intracellular pH regulation; cell proliferation; AntibodyArray; protein interaction; Srchomology 2 domain-containing protein tyrosine phosphatase

This article has been cited by other articles:

				E. Boedtkjer and C. Aalkjaer Insulin inhibits Na+/H+ exchange in vascular smooth muscle and endothelial cells in situ: involvement of H2O2 and tyrosine phosphatase SHP-2 Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H247 - H255. [Abstract] [Full Text] [PDF]

				E. K. Hoffmann, I. H. Lambert, and S. F. Pedersen Physiology of Cell Volume Regulation in Vertebrates Physiol Rev, January 1, 2009; 89(1): 193 - 277. [Abstract] [Full Text] [PDF]