PDE7A1, a cAMP-specific phosphodiesterase, inhibits cAMP-dependent protein kinase by a direct interaction with C

Ping Han, Pushpalatha Sonati, Charles Rubin, Tamar Michaeli

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The N-terminal regulatory region of the high affinity cAMP-specific phosphodiesterase, PDE7A1, contains two copies of the cAMP-dependent kinase (PKA) pseudosubstrate site RRGAI. In βTC3 insulinoma cells, PDE7A1 co-localizes with PKA II in the Golgi-centrosome region. The roles PDE7A1 and its regulatory region play in cAMP signaling were examined by studying interactions with PKA subunits. PDE7A1 associates with the dissociated C subunit of PKA (C), but does not bind tetrameric PKA holoenzyme. High affinity binding of C by PDE7A1 inhibits kinase activity in vitro (IC50 = 0.5 nM). The domain containing PKA pseudosubstrate sites at the N terminus of PDE7A1 mediates complex formation with C. The PDE7A1 N-terminal repeat region inhibits C activity in CHO-K1 cells and also suppresses C dependent, cAMP-independent, physiological responses in yeast. Thus, PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C. This study identifies a novel inhibitor of PKA and a non-catalytic affect of a cyclic nucleotide phosphodiesterase.

Original languageEnglish (US)
Pages (from-to)15050-15057
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number22
DOIs
StatePublished - Jun 2 2006

Fingerprint

Nucleic Acid Regulatory Sequences
Phosphoric Diester Hydrolases
Cyclic AMP-Dependent Protein Kinases
Phosphotransferases
Centrosome
Holoenzymes
Insulinoma
Terminal Repeat Sequences
CHO Cells
Cyclic Nucleotides
Yeast
Inhibitory Concentration 50
Yeasts
protein kinase modulator
In Vitro Techniques
Inhibition (Psychology)

ASJC Scopus subject areas

  • Biochemistry

Cite this

PDE7A1, a cAMP-specific phosphodiesterase, inhibits cAMP-dependent protein kinase by a direct interaction with C. / Han, Ping; Sonati, Pushpalatha; Rubin, Charles; Michaeli, Tamar.

In: Journal of Biological Chemistry, Vol. 281, No. 22, 02.06.2006, p. 15050-15057.

Research output: Contribution to journalArticle

Han, Ping ; Sonati, Pushpalatha ; Rubin, Charles ; Michaeli, Tamar. / PDE7A1, a cAMP-specific phosphodiesterase, inhibits cAMP-dependent protein kinase by a direct interaction with C. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 22. pp. 15050-15057.
@article{2f4267467d1444b0b07a247556992113,
title = "PDE7A1, a cAMP-specific phosphodiesterase, inhibits cAMP-dependent protein kinase by a direct interaction with C",
abstract = "The N-terminal regulatory region of the high affinity cAMP-specific phosphodiesterase, PDE7A1, contains two copies of the cAMP-dependent kinase (PKA) pseudosubstrate site RRGAI. In βTC3 insulinoma cells, PDE7A1 co-localizes with PKA II in the Golgi-centrosome region. The roles PDE7A1 and its regulatory region play in cAMP signaling were examined by studying interactions with PKA subunits. PDE7A1 associates with the dissociated C subunit of PKA (C), but does not bind tetrameric PKA holoenzyme. High affinity binding of C by PDE7A1 inhibits kinase activity in vitro (IC50 = 0.5 nM). The domain containing PKA pseudosubstrate sites at the N terminus of PDE7A1 mediates complex formation with C. The PDE7A1 N-terminal repeat region inhibits C activity in CHO-K1 cells and also suppresses C dependent, cAMP-independent, physiological responses in yeast. Thus, PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C. This study identifies a novel inhibitor of PKA and a non-catalytic affect of a cyclic nucleotide phosphodiesterase.",
author = "Ping Han and Pushpalatha Sonati and Charles Rubin and Tamar Michaeli",
year = "2006",
month = "6",
day = "2",
doi = "10.1074/jbc.M601333200",
language = "English (US)",
volume = "281",
pages = "15050--15057",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "22",

}

TY - JOUR

T1 - PDE7A1, a cAMP-specific phosphodiesterase, inhibits cAMP-dependent protein kinase by a direct interaction with C

AU - Han, Ping

AU - Sonati, Pushpalatha

AU - Rubin, Charles

AU - Michaeli, Tamar

PY - 2006/6/2

Y1 - 2006/6/2

N2 - The N-terminal regulatory region of the high affinity cAMP-specific phosphodiesterase, PDE7A1, contains two copies of the cAMP-dependent kinase (PKA) pseudosubstrate site RRGAI. In βTC3 insulinoma cells, PDE7A1 co-localizes with PKA II in the Golgi-centrosome region. The roles PDE7A1 and its regulatory region play in cAMP signaling were examined by studying interactions with PKA subunits. PDE7A1 associates with the dissociated C subunit of PKA (C), but does not bind tetrameric PKA holoenzyme. High affinity binding of C by PDE7A1 inhibits kinase activity in vitro (IC50 = 0.5 nM). The domain containing PKA pseudosubstrate sites at the N terminus of PDE7A1 mediates complex formation with C. The PDE7A1 N-terminal repeat region inhibits C activity in CHO-K1 cells and also suppresses C dependent, cAMP-independent, physiological responses in yeast. Thus, PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C. This study identifies a novel inhibitor of PKA and a non-catalytic affect of a cyclic nucleotide phosphodiesterase.

AB - The N-terminal regulatory region of the high affinity cAMP-specific phosphodiesterase, PDE7A1, contains two copies of the cAMP-dependent kinase (PKA) pseudosubstrate site RRGAI. In βTC3 insulinoma cells, PDE7A1 co-localizes with PKA II in the Golgi-centrosome region. The roles PDE7A1 and its regulatory region play in cAMP signaling were examined by studying interactions with PKA subunits. PDE7A1 associates with the dissociated C subunit of PKA (C), but does not bind tetrameric PKA holoenzyme. High affinity binding of C by PDE7A1 inhibits kinase activity in vitro (IC50 = 0.5 nM). The domain containing PKA pseudosubstrate sites at the N terminus of PDE7A1 mediates complex formation with C. The PDE7A1 N-terminal repeat region inhibits C activity in CHO-K1 cells and also suppresses C dependent, cAMP-independent, physiological responses in yeast. Thus, PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C. This study identifies a novel inhibitor of PKA and a non-catalytic affect of a cyclic nucleotide phosphodiesterase.

UR - http://www.scopus.com/inward/record.url?scp=33744959735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744959735&partnerID=8YFLogxK

U2 - 10.1074/jbc.M601333200

DO - 10.1074/jbc.M601333200

M3 - Article

VL - 281

SP - 15050

EP - 15057

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 22

ER -