cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1

Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2029-34. doi: 10.1073/pnas.252782799. Epub 2003 Feb 10.


The acid-sensing ion channel-1 (ASIC1) contributes to synaptic plasticity and may influence the response to cerebral ischemia and acidosis. We found that cAMP-dependent protein kinase phosphorylated heterologously expressed ASIC1 and endogenous ASIC1 in brain slices. ASIC1 also showed significant phosphorylation under basal conditions. Previous studies showed that the extreme C-terminal residues of ASIC1 bind the PDZ domain of the protein interacting with C-kinase-1 (PICK1). We found that protein kinase A phosphorylation of Ser-479 in the ASIC1 C terminus interfered with PICK1 binding. In contrast, minimizing phosphorylation or mutating Ser-479 to Ala enhanced PICK1 binding. Phosphorylation-dependent disruption of PICK1 binding reduced the cellular colocalization of ASIC1 and PICK1. Thus, the ASIC1 C terminus contains two sites that influence its binding to PICK1. Regulation of this interaction by phosphorylation provides a mechanism to control the cellular localization of ASIC1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Sensing Ion Channels
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Neurons / metabolism
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Sodium Channels / metabolism*


  • ASIC1 protein, human
  • ASIC1 protein, mouse
  • ASIC3 protein, human
  • Acid Sensing Ion Channels
  • Carrier Proteins
  • Cell Cycle Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Prkcabp protein, mouse
  • Sodium Channels
  • Cyclic AMP-Dependent Protein Kinases