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.
Department of Stomatology, University of California, San Francisco 94143, USA.
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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