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Activation of NHE3 by LPA is mediated by RSK2. This schematic model depicts how LPA regulates NHE3 in Caco-2bbe cells. Transactivation of EGF receptor (EGFR) by LPA5 activates RhoA- RhoA-Rho associated kinase (ROCK)-Pyk2 and ERK (45). The present study shows that Pyk2 and ERK phosphorylate RSK2, which in turn phosphorylates NHE3 at S663. This phosphorylation of NHE3 by RSK2 appears to be necessary for trafficking NHE3 to the apical membrane.
