Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1.

Thomas Jespersen; Bruno Gavillet; Miguel X van Bemmelen; Sophie Cordonier; Marc A Thomas; Olivier Staub; Hugues Abriel

doi:10.1016/j.bbrc.2006.08.014

Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1.

Thomas Jespersen, Bruno Gavillet, Miguel X van Bemmelen, Sophie Cordonier, Marc A Thomas, Olivier Staub, Hugues Abriel

Molecular Cardiology and Membrane Proteins

43 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Biochemical and Biophysical Research Communications
Volume	348
Issue number	4
Pages (from-to)	1455-62
Number of pages	7
ISSN	0006-291X
DOIs	https://doi.org/10.1016/j.bbrc.2006.08.014
Publication status	Published - 2006

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title = "Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1.",

abstract = "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.",

author = "Thomas Jespersen and Bruno Gavillet and {van Bemmelen}, {Miguel X} and Sophie Cordonier and Thomas, {Marc A} and Olivier Staub and Hugues Abriel",

note = "Keywords: Amino Acid Motifs; Binding Sites; Electric Conductivity; Humans; Muscle Proteins; Patch-Clamp Techniques; Protein Structure, Tertiary; Protein Tyrosine Phosphatase, Non-Receptor Type 3; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins c-fyn; Sequence Deletion; Sodium Channels; Two-Hybrid System Techniques",

year = "2006",

doi = "10.1016/j.bbrc.2006.08.014",

language = "English",

volume = "348",

pages = "1455--62",

journal = "Biochemical and Biophysical Research Communications",

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T1 - Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1.

AU - Jespersen, Thomas

AU - Gavillet, Bruno

AU - van Bemmelen, Miguel X

AU - Cordonier, Sophie

AU - Thomas, Marc A

AU - Staub, Olivier

AU - Abriel, Hugues

N1 - Keywords: Amino Acid Motifs; Binding Sites; Electric Conductivity; Humans; Muscle Proteins; Patch-Clamp Techniques; Protein Structure, Tertiary; Protein Tyrosine Phosphatase, Non-Receptor Type 3; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins c-fyn; Sequence Deletion; Sodium Channels; Two-Hybrid System Techniques

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1016/j.bbrc.2006.08.014

DO - 10.1016/j.bbrc.2006.08.014

M3 - Journal article

C2 - 16930557

SN - 0006-291X

VL - 348

SP - 1455

EP - 1462

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1.

Abstract

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