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.
Pubmed ID: 8901634
Proceedings of the National Academy of Sciences of the United States of America
October 29, 1996
- Agency: NIDDK NIH HHS, Id: DK 40259
- Agency: NIGMS NIH HHS, Id: GM 47413
- Amino Acid Sequence
- Arabidopsis Proteins
- Base Sequence
- Calcium-Binding Proteins
- GTP Phosphohydrolases
- Molecular Sequence Data
- Sequence Alignment
- Sodium-Hydrogen Antiporter