A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins

Randy A Hall; L S Ostedgaard; Richard T Premont; Jeremy T Blitzer; Nadeem  Rahman; M J Welsh; Robert J Lefkowitz

doi:10.1073/pnas.95.15.8496

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A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins

Journal article

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A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins

Randy A Hall, L S Ostedgaard, Richard T Premont, Jeremy T Blitzer, Nadeem Rahman, M J Welsh and Robert J Lefkowitz

Proceedings of the National Academy of Sciences - PNAS, Vol.95(15), pp.8496-8501

07/21/1998

DOI: 10.1073/pnas.95.15.8496

PMID: 9671706

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Abstract

The Na+/H+ exchanger regulatory factor (NHERF) binds to the tail of the beta2-adrenergic receptor and plays a role in adrenergic regulation of Na+/H+ exchange. NHERF contains two PDZ domains, the first of which is required for its interaction with the beta2 receptor. Mutagenesis studies of the beta2 receptor tail revealed that the optimal C-terminal motif for binding to the first PDZ domain of NHERF is D-S/T-x-L, a motif distinct from those recognized by other PDZ domains. The first PDZ domain of NHERF-2, a protein that is 52% identical to NHERF and also known as E3KARP, SIP-1, and TKA-1, exhibits binding preferences very similar to those of the first PDZ domain of NHERF. The delineation of the preferred binding motif for the first PDZ domain of the NHERF family of proteins allows for predictions for other proteins that may interact with NHERF or NHERF-2. For example, as would be predicted from the beta2 receptor tail mutagenesis studies, NHERF binds to the tail of the purinergic P2Y1 receptor, a seven-transmembrane receptor with an intracellular C-terminal tail ending in D-T-S-L. NHERF also binds to the tail of the cystic fibrosis transmembrane conductance regulator, which ends in D-T-R-L. Because the preferred binding motif of the first PDZ domain of the NHERF family of proteins is found at the C termini of a variety of intracellular proteins, NHERF and NHERF-2 may be multifunctional adaptor proteins involved in many previously unsuspected aspects of intracellular signaling.

Amino Acid Sequence

Humans

Molecular Sequence Data

Receptors, Purinergic P2Y1

Cystic Fibrosis Transmembrane Conductance Regulator - metabolism

Phosphoproteins - genetics

Cystic Fibrosis Transmembrane Conductance Regulator - chemistry

DNA Primers

Phosphoproteins - metabolism

Phosphoproteins - chemistry

Receptors, Adrenergic, beta-2 - metabolism

Receptors, Adrenergic, beta-2 - chemistry

Sodium-Hydrogen Exchangers - metabolism

Sequence Homology, Amino Acid

Receptors, Purinergic P2 - chemistry

Base Sequence

Receptors, Purinergic P2 - metabolism

Cloning, Molecular

Protein Binding

Details

Title: Subtitle: A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins
Creators: Randy A Hall - Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
L S Ostedgaard
Richard T Premont
Jeremy T Blitzer
Nadeem Rahman
M J Welsh
Robert J Lefkowitz
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.95(15), pp.8496-8501
DOI: 10.1073/pnas.95.15.8496
PMID: 9671706
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Grant note: HL42385 / NHLBI NIH HHS HL16037 / NHLBI NIH HHS R37 HL029851 / NHLBI NIH HHS R01 HL016037 / NHLBI NIH HHS HL29851 / NHLBI NIH HHS
Language: English
Date published: 07/21/1998
Academic Unit: Neurology; Molecular Physiology and Biophysics; Neurosurgery; Internal Medicine
Record Identifier: 9984020701202771

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