Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1.
In order to identify proteins interacting with the cardiac voltage-gated sodium channel Na(v)1.5, we used the last 66 amino acids of the C-terminus of the channel as bait to screen a human cardiac cDNA library. We identified the protein tyrosine phosphatase PTPH1 as an interacting protein. Pull-down experiments confirmed the interaction, and indicated that it depends on the PDZ-domain binding motif of Na(v)1.5. Co-expression experiments in HEK293 cells showed that PTPH1 shifts the Na(v)1.5 availability relationship toward hyperpolarized potentials, whereas an inactive PTPH1 or the tyrosine kinase Fyn does the opposite. The results of this study suggest that tyrosine phosphorylation destabilizes the inactivated state of Na(v)1.5.
Jespersen
Thomas
T
Department of Pharmacology and Toxicology, University of Lausanne, Switzerland.
Gavillet
Bruno
B
van Bemmelen
Miguel X
MX
Cordonier
Sophie
S
Thomas
Marc A
MA
Staub
Olivier
O
Abriel
Hugues
H
D020816:Amino Acid Motifs; D001665:Binding Sites; D004553:Electric Conductivity; D006801:Humans; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D017384:Sequence Deletion; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D051076:Proto-Oncogene Proteins c-fyn; C516656:PTPN3 protein, human; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3; D017027:Protein Tyrosine Phosphatases