A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange.
Activation of the ubiquitously expressed Na-H exchanger, NHE1, results in an increased efflux of intracellular H+. The increase in intracellular pH associated with this H+ efflux may contribute to regulating cell proliferation, differentiation, and neoplastic transformation. Although NHE1 activity is stimulated by growth factors and hormones acting through multiple GTPase-mediated pathways, little is known about how the exchanger is directly regulated. Using expression library screening, we identified a novel protein that specifically binds to NHE1 at a site that is critical for growth factor stimulation of exchange activity. This protein is homologous to calcineurin B and calmodulin and is designated CHP for calcineurin B homologous protein. Like NHE1, CHP is widely expressed in human tissues. Transient overexpression of CHP inhibits serum- and GTP-ase-stimulated NHE1 activity. CHP is a phosphoprotein and expression of constitutively activated GTPases decreases CHP phosphorylation. The phosphorylation state of CHP may therefore be an important signal controlling mitogenic regulation of NHE1.
Lin
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Department of Stomatology, University of California, San Francisco 94143, USA.
Barber
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D000595:Amino Acid Sequence; D029681:Arabidopsis Proteins; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016415:Sequence Alignment; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism
D029681:Arabidopsis Proteins; D002135:Calcium-Binding Proteins; D020558:GTP Phosphohydrolases; D017923:Sodium-Hydrogen Exchangers; C484078:CBL10 protein, Arabidopsis; C484079:CBL3 protein, Arabidopsis; C483419:calcineurin B-like protein 1, Arabidopsis; C480758:At5g55990 protein, Arabidopsis