Camp-Dependent Protein Kinase Phosphorylation of the Acid-Sensing Ion Channel-1 Regulates Its Binding to the Protein Interacting with C-Kinase-1
Document Type
Article
Publication Date
2-18-2003
Abstract
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.
DOI
10.1073/pnas.252782799
Montclair State University Digital Commons Citation
Leonard, A. Soren; Petroff, Elena; Hruska-Hageman, Alesia; Askwith, Candice C.; Price, Margaret P.; Wemmie, John A.; and Welsh, Michael J., "Camp-Dependent Protein Kinase Phosphorylation of the Acid-Sensing Ion Channel-1 Regulates Its Binding to the Protein Interacting with C-Kinase-1" (2003). Department of Biology Faculty Scholarship and Creative Works. 273.
https://digitalcommons.montclair.edu/biology-facpubs/273