Regulation of the Na+/H+ exchanger and signal transduction

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The Na/He exchanger (NHE) is an important regulator for intracellular pH (pH), C* volume, and transepithelial Na^+ transport. It exists in virtually all cells with cell ty* dependent pattern of isoform expression. Among six known isoforms of NHE, a ubiquito* isoform NHE1 is known to be rapidly activated in response to a variety of extracellul* stimuli ranging from growth factors to mechanical stimuli such as hyperosmotic stress a* cell spreading. Some accessory regulatory factors has been suggested to be involved in * regulation of NHE1. Galmodulin is the first identified regulatory factor that is involved Ca^<2+>-induced activation of NHE1. Recently, the calcineurin B homologous protein (CHP) h* been cloned as a candidate for such regulatory factors of NHE1. In recent two years, w* tried to identify CHP binding domain within NHE1. A cytoplasmic region of aa 515-530 w* identified as a strong CHP-binding domain. However, we have not yet determine t* precise role of CHP in the regulation of NHE1. We also tried to identify an important regi* of NHE for volume regulation and found that the first extracellular loop is a critical region f* positive or negative response to volume change in NHE isoforms.