Na-H Exchangers and Intracellular pH Regulation

Re: symposium 246

On Fri Dec 4, grover wrote
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>Dr. Haworth: Hope you are enjoying the meeting. Great poster. Three questions. First, are the consensus sequence for PKD present in all the NHE isoforms? Second, what is the tissue distribution of PKD? Third, is PKD activation liked to the same G-proteins as the other isoforms of PKC?
>Dr. Grover: Thanks for your comments. Answers to your questions:
1. Yes. We hadn't really considered any of the other NHE isoforms as potential PKD targets, as our work is exclusively in COS cells and cardiac myocytes, which only express NHE1 (plasma membrane) and presumably NHE6 (mitochondrial?). Looking at the rat NHE1-4 sequences, there are several potential sites for PKD phosphorylation in each isoform. I don't have any information on NHE5 or 6.
2. PKD seems to be universally distributed, as is NHE1.
3. PKD is activated both in parallel with and downstream of PKC. Zugaza et al (EMBO J 1996 v15 pp6220-6230) showed that constitutively active PKC beta1, epsilon and eta activate PKD, while PKC zeta does not, so anything which activates beta, epsilon and eta will activate PKD, as will production of diacylglycerol. Endothelin, PDGF and norepinephrine are known to activate PKD in COS cells or cultured neonatal myocytes.

Thu Dec 10