Phosphorylation of the Third Intracellular Loop of the Mouse α 1b -Adrenergic Receptor by cAMP-dependent Protein Kinase

1. Previous studies have shown that beta-adrenergic receptor activation has many effects on neuronal function in hippocampal area CA1. However, all of the physiological effects of beta-adrenergic receptor activation in this region reported to date have been attributed to postsynaptic mechanisms. A series of studies was performed to test the hypothesis that beta-adrenergic receptor activation also acts presynaptically to enhance excitatory synaptic transmission. 2. Application of the selective beta-adrenergic agonist isoproterenol to hippocampal slices induced an increase in the amplitude of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal cells. This response was potentiated in the presence of a cyclic nucleotide phosphodiesterase inhibitor. Isoproterenol also resulted in the appearance of a late inward synaptic current that likely represents polysynaptically evoked EPSCs. Both the increased amplitude of the monosynaptic EPSC and the appearance of polysynaptic EPSCs in response to isoproterenol were blocked by H89, an inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. 3. Isoproterenol induced an increase in the frequency of spontaneous miniature EPSCs but did not affect the amplitude of these currents. In addition, isoproterenol had no effect on currents elicited by direct application of the ionotropic glutamate receptor agonist, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 4. These results suggest that activation of presynaptic beta-adrenergic receptors enhances synaptic transmission in area CA1 via activation of cAMP-dependent protein kinase.

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Subcellular distribution and activation of rat submandibular cAMP-dependent protein kinase following β-adrenergic receptor stimulation

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/0167-4889(88)90084-5 ◽

1988 ◽

Vol 969 (1) ◽

pp. 28-32 ◽

Cited By ~ 9

Author(s):

David O. Quissell ◽

Lynn M. Deisher ◽

Katherine A. Barzen

Keyword(s):

Protein Kinase ◽

Subcellular Distribution ◽

Adrenergic Receptor ◽

Receptor Stimulation ◽

Dependent Protein Kinase ◽

Camp Dependent Protein Kinase ◽

Dependent Protein

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5' flanking sequence and structure of a gene encoding rat 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.86.17.6543 ◽

1989 ◽

Vol 86 (17) ◽

pp. 6543-6547 ◽

Cited By ~ 42

Author(s):

M I Darville ◽

K M Crepin ◽

L Hue ◽

G G Rousseau

Keyword(s):

Protein Kinase ◽

Codon Position ◽

Bifunctional Enzyme ◽

Flanking Sequence ◽

Dependent Protein Kinase ◽

Gene Encoding ◽

The Third ◽

Camp Dependent Protein Kinase ◽

Dependent Protein ◽

Synthesis And Degradation

The synthesis and degradation of fructose 2,6-bisphosphate, a ubiquitous stimulator of glycolysis, are catalyzed by 6-phosphofructo-2-kinase (EC 2.7.1.105) and fructose-2,6-bisphosphatase (EC 3.1.3.46), respectively. In liver, these two activities belong to separate domains of the same 470-residue polypeptide. Various mRNAs have been described for this bifunctional enzyme, which is controlled by hormonal and metabolic signals. To understand the origin and regulation of these mRNAs, we have characterized rat genomic clones encoding the liver isozyme, which is regulated by cAMP-dependent protein kinase, and the muscle isozyme, which is not. We describe here a 55-kilobase gene that encodes these isozymes by alternative splicing from two promoters. Each of the putative promoters was sequenced over about 3 kilobases and found to include nucleotide motifs for binding regulatory factors. The two isozymes share the same 13 exons and differ only by the first exon that, in the liver but not in the muscle isozyme, contains the serine phosphorylated by cAMP-dependent protein kinase. The gene was assigned to the X chromosome. An analysis of the exon limits of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in relation to its functional domains and to its similarity with other proteins plus its G + C content at the third codon position suggests that this gene originates from several fusion events.

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Assembly of an SAP97-AKAP79-cAMP-dependent Protein Kinase Scaffold at the Type 1 PSD-95/DLG/ZO1 Motif of the Human β1-Adrenergic Receptor Generates a Receptosome Involved in Receptor Recycling and Networking

Journal of Biological Chemistry ◽

10.1074/jbc.m608871200 ◽

2006 ◽

Vol 282 (7) ◽

pp. 5085-5099 ◽

Cited By ~ 57

Author(s):

Lidia A. Gardner ◽

Anjaparavanda P. Naren ◽

Suleiman W. Bahouth

Keyword(s):

Protein Kinase ◽

Adrenergic Receptor ◽

Carboxyl Terminus ◽

Intracellular Loop ◽

Dependent Protein Kinase ◽

Anchoring Protein ◽

Dependent Protein ◽

Binding Sequence ◽

Maguk Protein

Appropriate trafficking of the β1-adrenergic receptor (β1-AR) after agonist-promoted internalization is crucial for the resensitization of its signaling pathway. Efficient recycling of the β1-AR required the binding of the protein kinase A anchoring protein-79 (AKAP79) to the carboxyl terminus of the β1-AR (Gardner, L. A., Tavalin, S. A., Goehring, A., Scott, J. D., and Bahouth, S. W. (2006) J. Biol. Chem. 281, 33537-33553). In this study we show that AKAP79 forms a complex with the type 1 PDZ-binding sequence (ESKV) at the extreme carboxyl terminus of the β1-AR, which is mediated by the membrane-associated guanylate kinase (MAGUK) protein SAP97. Thus, the PDZ and its associated SAP97-AKAP79 complex are involved in targeting the cyclic AMP-dependent protein kinase (PKA) to the β1-AR. The PDZ and its scaffold were required for efficient recycling of the β1-AR and for PKA-mediated phosphorylation of the β1-AR at Ser312. Overexpression of the catalytic subunit of PKA or mutagenesis of Ser312 to the phosphoserine mimic aspartic acid both rescued the recycling of the trafficking-defective β1-ARΔ PDZ mutant. Thus, trafficking signals transmitted from the PDZ-associated scaffold in the carboxyl terminus of the β1-AR to Ser312 in the 3rd intracellular loop (3rd IC) were paramount in setting the trafficking itinerary of the β1-AR. The data presented here show that a novel β1-adrenergic receptosome is organized at the β1-AR PDZ to generate a scaffold essential for trafficking and networking of the β1-AR.

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