AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex

I. Jo, D. T. Ward, M. A. Baum, J. D. Scott, V. M. Coghlan, T. G. Hammond, H. W. Harris

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

We have demonstrated that inner medullary collecting duct (IMCD) heavy endosomes purified from rat kidney IMCD contain the type II protein kinase A (PKA) regulatory subunit (RII), protein phosphatase (PP)2B, PKCζ, and an RII-binding protein (relative molecular mass ∼90 kDa) representing a putative A kinase anchoring protein (AKAP). Affinity chromatography of detergent-solubilized endosomes on cAMP-agarose permits recovery of a protein complex consisting of the 90-kDa AKAP, RII, PP2B, and PKCζ. With the use of small-particle flow cytometry, RII and PKCζ were localized to an identical population of endosomes, suggesting that these proteins are components of an endosomal multiprotein complex. 32P-labeled aquaporin-2 (AQP2) present in these PKA-phosphorylated endosomes was dephosphorylated in vitro by either addition of exogenous PP2B or by an endogenous endosomal phosphatase that was inhibited by the PP2B inhibitors EDTA and the cyclophilin-cyclosporin A complex. We conclude that IMCD heavy endosomes possess an AKAP multiprotein-signaling complex similar to that described previously in hippocampal neurons. This signaling complex potentially mediates the phosphorylation of AQP2 to regulate its trafficking into the IMCD apical membrane. In addition, the PP2B component of the AKAP-signaling complex could also dephosphorylate AQP2 in vivo.

Original languageEnglish
Pages (from-to)F958-F965
JournalAmerican Journal of Physiology - Renal Physiology
Volume281
Issue number5 50-5
DOIs
StatePublished - 2001

Keywords

  • A kinase anchoring protein
  • Adenosine 3′,5′-cyclic monophosphate
  • Aquaporin-2
  • Kidney
  • Protein phosphatase 2B
  • Water channel

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