Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit: A type II cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a higher affinity for cAMP than that of the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIIBETA SUBUNIT. Binding of this subunit by A KINASE ANCHOR PROTEINS may play a role in the cellular localization of type II protein kinase A.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Cyclic AMP-Dependent Protein Kinase Type II: A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Cyclic AMP-Dependent Protein Kinase RIalpha Subunit: A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.Calcium-Calmodulin-Dependent Protein Kinase Type 1: A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.A Kinase Anchor Proteins: A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.Kinetics: The rate dynamics in chemical or physical systems.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit: A type II cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIIALPHA SUBUNIT. Binding of this subunit by A KINASE ANCHOR PROTEINS may play a role in the cellular localization of type II protein kinase A.Paramecium tetraurelia: A species of ciliate protozoa. It is used in biomedical research.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Adrenal Cortex Diseases: Pathological processes of the ADRENAL CORTEX.Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the ENDOCRINE SYSTEM.Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Water: A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Triacetoneamine-N-Oxyl: Cyclic N-oxide radical functioning as a spin label and radiation-sensitizing agent.Motion: Physical motion, i.e., a change in position of a body or subject as a result of an external force. It is distinguished from MOVEMENT, a process resulting from biological activity.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).

Conservation and function of a bovine sperm A-kinase anchor protein homologous to mouse AKAP82. (1/68)

Protein kinase A regulates sperm motility through the cAMP-dependent phosphorylation of proteins. One mechanism to direct the activity of the kinase is to localize it near its protein substrates through the use of anchoring proteins. A-Kinase anchoring proteins (AKAPs) act by binding the type II regulatory subunit of protein kinase A and tethering it to a cellular organelle or cytoskeletal element. We showed previously that mAKAP82, the major protein of the fibrous sheath of the mouse sperm flagellum, is an AKAP. The available evidence indicates that protein kinase A is compartmentalized to the fibrous sheath by binding mAKAP82. To characterize AKAP82 in bovine sperm, a testicular cDNA library was constructed and used to isolate a clone encoding bAKAP82, the bovine homologue. Sequence analysis showed that the primary structure of bAKAP82 was highly conserved. In particular, the amino acid sequence corresponding to the region of mAKAP82 responsible for binding the regulatory subunit of protein kinase A was identical in the bull. Bovine AKAP82 was present in both epididymal and ejaculated sperm and was localized to the entire principal piece of the flagellum, the region in which the fibrous sheath is located. Finally, bAKAP82 bound the regulatory subunit of protein kinase A. These data support the idea that bAKAP82 functions as an anchoring protein for the subcellular localization of protein kinase A in the flagellum.  (+info)

Generation of a novel A kinase anchor protein and a myristoylated alanine-rich C kinase substrate-like analog from a single gene. (2/68)

A unique Drosophila gene encodes two novel signaling proteins. Drosophila A kinase anchor protein 200 (DAKAP200) (753 amino acids) binds regulatory subunits of protein kinase AII (PKAII) isoforms in vitro and in intact cells. The acidic DAKAP200 polypeptide (pI approximately 3.8) contains an optimal N-terminal myristoylation site and a positively charged domain that resembles the multifunctional phosphorylation site domain of vertebrate myristoylated alanine-rich C kinase substrate proteins. The 15-kilobase pair DAKAP200 gene contains six exons and encodes a second protein, DeltaDAKAP200. DeltaDAKAP200 is derived from DAKAP200 transcripts by excision of exon 5 (381 codons), which encodes the PKAII binding region and a Pro-rich sequence. DeltaDAKAP200 appears to be a myristoylated alanine-rich C kinase substrate analog. DAKAP200 and DeltaDAKAP200 are evident in vivo at all stages of Drosophila development. Thus, both proteins may play important physiological roles throughout the life span of the organism. Nevertheless, DAKAP200 gene expression is regulated. Maximal levels of DAKAP200 are detected in the pupal phase of development; DeltaDAKAP200 content is elevated 7-fold in adult head (brain) relative to other body parts. Enhancement or suppression of exon 5 excision during DAKAP200 pre-mRNA processing provides potential mechanisms for regulating anchoring of PKAII and targeting of cAMP signals to effector sites in cytoskeleton and/or organelles.  (+info)

A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes. (3/68)

The specificity of intracellular signaling events is controlled, in part, by compartmentalization of protein kinases and phosphatases. The subcellular localization of these enzymes is often maintained by protein- protein interactions. A prototypic example is the compartmentalization of the cAMP-dependent protein kinase (PKA) through its association with A-kinase anchoring proteins (AKAPs). A docking and dimerization domain (D/D) located within the first 45 residues of each regulatory (R) subunit protomer forms a high affinity binding site for its anchoring partner. We now report the structures of two D/D-AKAP peptide complexes obtained by solution NMR methods, one with Ht31(493-515) and the other with AKAP79(392-413). We present the first direct structural data demonstrating the helical nature of the peptides. The structures reveal conserved hydrophobic interaction surfaces on the helical AKAP peptides and the PKA R subunit, which are responsible for mediating the high affinity association in the complexes. In a departure from the dimer-dimer interactions seen in other X-type four-helix bundle dimeric proteins, our structures reveal a novel hydrophobic groove that accommodates one AKAP per RIIalpha D/D.  (+info)

Binding of PKA-RIIalpha to the Adenovirus E1A12S oncoprotein correlates with its nuclear translocation and an increase in PKA-dependent promoter activity. (4/68)

The adenovirus type 12 (Ad12) E1A12S oncoprotein utilizes the cAMP/protein kinase A (PKA) signal transduction pathway to activate expression of the viral E2 gene, the products of which are essential for viral replication. A central unsolved question is, however, whether E1A12S interacts directly with PKA in the process of promoter activation. We show here that E1A12S binds to the regulatory subunits (R) of PKA in vitro and in vivo. Interaction depends on the N-terminus and the conserved region 1 (CR1) of E1A12S. Both domains are also essential for the activation of viral E2 gene expression. Infection of cells with Ad12 leads to the cellular redistribution of RIIalpha from the cytoplasm into the nucleus. Furthermore, RIIalpha is also located in the nucleus of cells transformed by E1 of Ad12 and transient expression of E1A12S leads to the redistribution of RIIalpha into the nucleus in a N-terminus- and CR1-dependent manner. Cotransfection of E1A12S with RIIalpha results in strong activation of the E2 promoter. Based on these results we conclude that E1A12S functions as a viral A-kinase anchoring protein redistributing RIIalpha from the cytoplasm into the nucleus where it is involved in E1A12S-mediated activation of the E2 promoter.  (+info)

CDK1-mediated phosphorylation of the RIIalpha regulatory subunit of PKA works as a molecular switch that promotes dissociation of RIIalpha from centrosomes at mitosis. (5/68)

Protein kinase A regulatory subunit RIIalpha is tightly bound to centrosomal structures during interphase through interaction with the A-kinase anchoring protein AKAP450, but dissociates and redistributes from centrosomes at mitosis. The cyclin B-p34(cdc2) kinase (CDK1) has been shown to phosphorylate RIIalpha on T54 and this has been proposed to alter the subcellular localization of RIIalpha. We have made stable transfectants from an RIIalpha-deficient leukemia cell line (Reh) that expresses either wild-type or mutant RIIalpha (RIIalpha(T54E)). When expressed, RIIalpha detaches from centrosomes at mitosis and dissociates from its centrosomal location in purified nucleus-centrosome complexes by incubation with CDK1 in vitro. By contrast, centrosomal RIIalpha(T54E) is not redistributed at mitosis, remains mostly associated with centrosomes during all phases of the cell cycle and cannot be solubilized by CDK1 in vitro. Furthermore, RIIalpha is solubilized from particular cell fractions and changes affinity for AKAP450 in the presence of CDK1. D and V mutations of T54 also reduce affinity for the N-terminal RII-binding domain of AKAP450, whereas small neutral residues do not change affinity detected by surface plasmon resonance. In addition, only RIIalpha(T54E) interacts with AKAP450 in a RIPA-soluble extract from mitotic cells. Finally, microtubule repolymerization from mitotic centrosomes of the RIIalpha(T54E) transfectant is poorer and occurs at a lower frequency than that of RIIalpha transfectants. Our results suggest that T54 phosphorylation of RIIalpha by CDK1 might serve to regulate the centrosomal association of PKA during the cell cycle.  (+info)

Regulation of anchoring of the RIIalpha regulatory subunit of PKA to AKAP95 by threonine phosphorylation of RIIalpha: implications for chromosome dynamics at mitosis. (6/68)

CDK1 phosphorylates the A-kinase regulatory subunit RIIalpha on threonine 54 (T54) at mitosis, an event proposed to alter the subcellular localization of RIIalpha. Using an RIIalpha-deficient leukemic cell line (Reh) and stably transfected Reh cell clones expressing wild-type RIIalpha or an RIIalpha(T54E) mutant, we show that RIIalpha associates with chromatin-bound A-kinase anchoring protein AKAP95 at mitosis and that this interaction involves phosphorylation of RIIalpha on T54. During interphase, both RIIalpha and RIIalpha(T54E) exhibit a centrosome-Golgi localization, whereas AKAP95 is intranuclear. At mitosis and in a mitotic extract, most RIIalpha, but not RIIalpha(T54E), co-fractionates with chromatin, onto which it associates with AKAP95. This correlates with T54 phosphorylation of RIIalpha. Disrupting AKAP95-RIIalpha anchoring or depleting RIIalpha from the mitotic extract promotes premature chromatin decondensation. In a nuclear reconstitution assay that mimics mitotic nuclear reformation, RIIalpha is threonine dephosphorylated and dissociates from AKAP95 prior to assembly of nuclear membranes. Lastly, the Reh cell line exhibits premature chromatin decondensation in vitro, which can be rescued by addition of wild-type RIIalpha or an RIIalpha(T54D) mutant, but not RIIalpha(T54E, A, L or V) mutants. Our results suggest that CDK1-mediated T54 phosphorylation of RIIalpha constitutes a molecular switch controlling anchoring of RIIalpha to chromatin-bound AKAP95, where the PKA-AKAP95 complex participates in remodeling chromatin during mitosis.  (+info)

Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A. (7/68)

Integrin receptor activation is an important regulatory mechanism for cell-substrate and cell-cell adhesion. In this study, we explore a signaling pathway activated by mAb 12G10, an antibody that can activate beta(1) integrins and induce integrin-mediated cell-cell and cell-substrate adhesion. We have found that the cAMP-dependent protein kinase (PKA) is required for both mAb 12G10-induced cell-cell and cell-substrate adhesion of HT-1080 cells. Binding of mAb 12G10 to beta(1) integrins stimulates an increase in intracellular cAMP levels and PKA activity, and a concomitant shift in the localization of the PKA type II regulatory subunits from the cytoplasm to areas where integrins expressing the 12G10 epitope are located. MAb 12G10-induced cell-cell adhesion was mimicked by a combination of clustering beta(1) integrins and elevating PKA activity with Sp-adenosine-3',5'-cyclic monophosphorothioate or forskolin. We also show that two processes required for HT-1080 cell-cell adhesion, integrin clustering and F-actin polymerization are both dependent on PKA. Taken together, our data suggest that PKA plays a key role in the signaling pathway, resulting from activation of beta(1) integrins, and that this enzyme may be required for upregulation of cell-substrate and cell-cell adhesion.  (+info)

Evidence for involvement of A-kinase anchoring protein in activation of rat arterial K(ATP) channels by protein kinase A. (8/68)

1. We have investigated the possible role of A-kinase anchoring proteins (AKAPs) in protein kinase A (PKA) signalling to ATP-sensitive K+ (K(ATP)) channels of rat isolated mesenteric arterial smooth muscle cells using whole-cell patch clamp and peptides that inhibit PKA-AKAP binding. 2. Intracellular Ht31 peptide (20 microM), which inhibits the PKA-AKAP interaction, blocked K(ATP) current activation by either dibutyryl cAMP or calcitonin gene-related peptide. Ht31-proline (20 microM), which does not inhibit PKA binding to AKAP, did not block K(ATP) current activation. 3. Ht31 reduced K(ATP) current activated by pinacidil and also prevented its inhibition by Rp-cAMPS, effects consistent with Ht31 blocking steady-state K(ATP) channel activation by PKA. However, Ht31 did not prevent K(ATP) current activation by the catalytic subunit of PKA. 4. An antibody to the RII subunit of PKA showed localization of PKA near to the cell membrane. Our results provide evidence that both steady-state and receptor-driven activation of K(ATP) channels by PKA involve the localization of PKA by an AKAP.  (+info)

*PRKAR2A

... type-II regulatory subunit of cyclic-AMP-dependent protein kinase by glycogen synthase kinase 3 and glycogen synthase kinase 5 ... and characterization of subunits of cAMP-dependent protein kinase in human testis. Reverse mobilities of human RII alpha and ... "MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". ... "Ezrin is a cyclic AMP-dependent protein kinase anchoring protein". The EMBO Journal. 16 (1): 35-43. doi:10.1093/emboj/16.1.35. ...
TY - JOUR. T1 - Purification of a regulatory subunit of type II cAMP-dependent protein kinase from Drosophila heads. AU - Inoue, Hiroko. AU - Yoshioka, Tohru. PY - 1997/6/9. Y1 - 1997/6/9. N2 - The cytosolic extract from Drosophila heads was separated using anion-exchange column chromatography. Two types of cAMP-dependent protein kinase (PKA), type I and type II, were detected, and type II PKA was found to be a major isozyme. The regulatory subunit of type II PKA (RII) was purified, and only one isoform was observed. The purified protein had an apparent molecular mass of 51 kDa on SDS gel electrophoresis. Partial amino acid sequences of the protein were almost identical with the RIIα subunit of human. Since PKA has been implicated to be especially important for learning and memory in Drosophila, the RII subunit may play an essential role in the regulation of neuronal activity in the brain of Drosophila, and possibly in human.. AB - The cytosolic extract from Drosophila heads was separated using ...
Our results provide evidence that PKA remains anchored to AKAPs in vivo in RIIα knockout mouse skeletal muscle and that this anchoring sustains the PKA-dependent potentiation of the L-type Ca2+ channel. These results challenge the idea that type II regulatory subunits are required for anchoring of PKA in vivo and raise the possibility that RIα can also serve in this capacity. Immunocytochemical studies show that the C subunit of the type I holoenzyme in RIIα knockout skeletal muscle is colocalized in transverse tubules with the L-type Ca2+ channel, consistent with anchoring of type I PKA with Ca2+ channels. In vitro measurements of RIα binding affinity to Ht31 demonstrate that RIα binds to AKAPs with a 500-fold lower affinity than RIIα, but this low affinity is apparently sufficient for anchoring in vivo. Previous reports have estimated the intracellular concentration of PKA to be in the 1 μM range, which would lead to significant binding at the Kd measured by surface plasmon resonance. ...
CRC is the third leading cause of mortality in men and women worldwide [1]. Most of the cancer-related deaths in CRC patients are as a result of early spread of cancer cells or due to reoccurrence post-surgical interventions [15]. Alterations in some key regulatory molecules involved in cell cycle, apoptosis and EMT pathways have been proposed in the initiation of carcinogenesis [16]. In this context, efforts are being made to identify and characterize tumor associated molecules for development of therapeutic targets for cancer treatment. A unique class of tumor associated antigens called cancer testis (CT) antigens has been reported in various malignancies and have been shown to be associated with tumor growth and metastasis [4]. Only few CT antigens with abundant expression, namely sperm associated antigen (SPAG9) and AKAP4 have been shown to be associated with CRC [5, 10]. In this study, we examined the involvement of AKAP4 in various malignant properties at phenotype and molecular level of ...
MSSGRRRGSAPWHSFSRFFAPRSPSRDKEEEEEERPGTSPPPAPGRSAASVENEPMSTSQKKENVLSSEA 1 - 70 VKIRQSEDKRNHAEKPVTLPVQEDPKKAYDLSSSTSDTKIGESDRQPKESFFQFLGNLFNISGKSSLGEA 71 - 140 KQSSFKDDQDKTEKDLQNPSDHHEDGIKREREIFSGSLRTQTHPTEEQDSNSSELSDAFSLDTTQDSDQE 141 - 210 TTNLLKQIDGKPEKPSVTYATYRGPRHIGKYLKQQTGLATVNTLDRENESSDSSTNRHIDPGSEIEAGVL 211 - 280 PLLLSASTDSSMKGNLLEGPLEDSDCSKTSFNKENSLTNNPELQNIASSNNLLNKNAWGSIERNRSSPSS 281 - 350 VTNSSYDGESDSQHHLSCEPVSQTNRNLVCSALLTGSNHRKVPCSPDFQRVTTTENTIKENSTVMSNRTL 351 - 420 VQREELVEPQGPAISDFSCSKSDGSDTTEQESTNLPSPNKSIRHEHLQLPESECSDKQTIDSSSKQAATH 421 - 490 TNIIALQRHAVTDTEFVNEGKRLSAQDSQKNVAVREIRRETESASAGESIASSHVKAPEDKIESLPKDTD 491 - 560 QYFETKAKKLDFRSHDKIPHIRMNKKDLASLNYISESAVVASLGNENAPELKFELNRSHISETPLDSESP 561 - 630 QQAEVSPDAKTSLSLDCKKLNFSISPPTFVSGVGMLSKLDIPDLMNEGSPVPIETGNVNIVGISYQPRKC 631 - 700 KEENVKNHVEAAGRKSPPPSFCLEYTSAIFEFKEVLSNSEKCQVLPGSEASGPHLTGLELLSFDSGNLSK 701 - 770 DCSSILSQDPNRVELVSSNTKANMSIIEKSDSLSLEAKTANIVSKAEIDGQNNVLVESHSGRGKTISLSK 771 - 840 ...
1. CukkemaneA, SeifertR, KauppUB (2011) Cooperative and uncooperative cyclic-nucleotide-gated ion channels. Trends Biochem Sci 36: 55-64.. 2. KauppUB, NiidomeT, TanabeT, TeradaS, BönigkW, et al. (1989) Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342: 762-766.. 3. LudwigA, ZongX, JeglitschM, HofmannF, BielM (1998) A family of hyperpolarization-activated mammalian cation channels. Nature 393: 587-591.. 4. TakioK, SmithSB, KrebsEG, WalshKA, TitaniK (1982) Primary structure of the regulatory subunit of type II cAMP-dependent protein kinase from bovine cardiac muscle. Proc Natl Acad Sci USA 79: 2544-2548.. 5. TakioK, WadeRD, SmithSB, KrebsEG, WalshKA, et al. (1984) Guanosine cyclic 3′,5′-phosphate dependent protein kinase, a chimeric protein homologous with two separate protein families. Biochemistry 23: 4207-4218.. 6. de RooijJ, ZwartkruisFJ, VerheijenMH, CoolRH, NijmanSM, et al. (1998) Epac is a Rap1 ...
RecName: Full=A-kinase anchor protein 13; Short=AKAP-13;AltName: Full=Protein kinase A-anchoring protein 13;AltName: Full=Breast cancer nuclear receptor-binding auxiliary protein;AltName: Full=Human thyroid-anchoring protein 31;AltName: Full=Guanine nucleotide exchange factor Lbc;AltName: Full=AKAP-Lbc;AltName: Full=P47;AltName: Full=Lymphoid blast crisis oncogene; Short=LBC oncogene;AltName: Full=Non-oncogenic Rho GTPase-specific GTP exchange ...
This gene encodes a member of A-kinase anchoring proteins (AKAPs), a family of functionally related proteins that target protein kinase A to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. It has been reported that this protein is important for maintaining heart rate and myocardial contractility through its targeting of protein kinase A. In mouse, defects of this gene lead to cardiac arrhythmias and premature death. In humans, polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2013 ...
AKAP7 - AKAP7 (untagged)-Human A kinase (PRKA) anchor protein 7 (AKAP7), transcript variant beta available for purchase from OriGene - Your Gene Company.
Akap1 - Akap1 (untagged) - Mouse A kinase (PRKA) anchor protein 1 (Akap1), nuclear gene encoding mitochondrial protein, transcript variant 1, (10ug) available for purchase from OriGene - Your Gene Company.
Homo sapiens A kinase (PRKA) anchor protein (gravin) 12 (AKAP12), transcript variant 1, mRNA. (H00009590-R01) - Products - Abnova
Looking for online definition of A kinase (PRKA) anchor protein 6 in the Medical Dictionary? A kinase (PRKA) anchor protein 6 explanation free. What is A kinase (PRKA) anchor protein 6? Meaning of A kinase (PRKA) anchor protein 6 medical term. What does A kinase (PRKA) anchor protein 6 mean?
cAMP signals are locally amplified by scaffold proteins (A Kinase Anchor Proteins, AKAPs) that tether cAMP-dependent Protein Kinase A (PKA) to discrete cellular locations. Here we hypothesized that mitochondrial anchoring of PKA promotes survival in muscle cells. We identified AKAP121 as the major mitochondrial AKAP in cardiomyocytes and aortic smooth muscle cells. In response to pressure overload, cardiac AKAP121 levels were significantly reduced, inducing marked mitochondrial dysfunction, DNA damage and activation of the DNA repair machinery. To test the role of AKAP121 in the modulation of cell survival, we synthesized peptides (AK-in) containing AKAP121 mitochondrial targeting domain but lacking its PKA binding motif, in order to competitively displace the endogenous AKAP121/PKA complex from mitochondria. Sequence-scrambled peptides were synthetized and used as controls (S). 24 hours after administration, FITC-conjugated AK-in peptides co-localized with mitochondria at confocal microscopy; ...
Complete information for AKAP12 gene (Protein Coding), A-Kinase Anchoring Protein 12, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for AKAP7 gene (Protein Coding), A-Kinase Anchoring Protein 7, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The acknowledged potential of small-molecule therapeutics targeting disease-related protein-protein interactions (PPIs) has promoted active research in this field. The strategy of using small molecule inhibitors (SMIs) to fight strong (tight-binding) PPIs tends to fall short due to the flat and wide interfaces of PPIs. Here we propose a biligand approach for disruption of strong PPIs. The potential of this approach was realized for disruption of the tight-binding (KD = 100 pM) tetrameric holoenzyme of cAMP-dependent protein kinase (PKA). Supported by X-ray analysis of cocrystals, bifunctional inhibitors (ARC-inhibitors) were constructed that simultaneously associated with both the ATP-pocket and the PPI interface area of the catalytic subunit of PKA (PKAc). Bifunctional inhibitor ARC-1411, possessing a KD value of 3 pM toward PKAc, induced the dissociation of the PKA holoenzyme with a low-nanomolar IC50, whereas the ATP-competitive inhibitor H89 bound to the PKA holoenzyme without disruption of the

obesity  - BioMedLib™ search engineobesity - BioMedLib™ search engine

Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; EC 2.7.11.11 / Cyclic AMP-Dependent Protein Kinases ... The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular ... Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet- ... Title] Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to ...
more infohttp://bmlreview.com/?kwr=obesity&smntc=governmental+or+regulatory+activity&kwr=&ck=&cxts=10&fntszff=100&hghlght=maroon&srtrdr=relevance&annttn=none&pdthm=2010&hqryhstry=5062b3f288e4d101&pgwdth=100&mld=&wft=wims&b4s=469216088

Tore Jahnsen
       - Institutt for medisinske basalfagTore Jahnsen - Institutt for medisinske basalfag

Solberg, Rigmor & Jahnsen, Tore (1994). Human type I regulatory subunits of cyclic AMP-dependent protein kinases. Structure, ... and characterization of subunits of cAMP-dependent protein kinase in human testis. Reverse mobilities of human RII alpha and ... Cyclic AMP-dependent protein kinase (vertebrates), In G. Hardie & S. Hanks (ed.), The Protein Kinase FactsBook. Elsevier. ISBN ... and regulation of cyclic AMP-dependent protein kinases. * Skålhegg, Bjørn Steen & Jahnsen, Tore (1993). Isozymes of cyclic AMP- ...
more infohttps://www.med.uio.no/imb/personer/vit/torej/index.html

SMART: Secondary literature for RIIa domainSMART: Secondary literature for RIIa domain

Cyclic AMP-dependent protein kinase is tethered to protein kinase A anchoring proteins (AKAPs) through regulatory subunits (R) ... with A-kinase anchoring proteins (AKAPs). Using an interaction cloning strategy with RIIalpha as a probe, we have isolated ... of the cyclic AMP-dependent protein kinase (cAPK), the heat-stable protein kinase inhibitors (PKIs) and the regulatory (R) ... A-kinase anchoring proteins (AKAPs) bind to the regulatory subunit of cAMP-dependent protein kinase (PKA) to direct the kinase ...
more infohttp://smart.embl-heidelberg.de/smart/show_secondary.cgi?domain=RIIa

Oculocutaneous Albinism
      - Albinism, Yellow Mutant
     Summary Report | CureHunterOculocutaneous Albinism - Albinism, Yellow Mutant Summary Report | CureHunter

Cyclic AMP-Dependent Protein Kinase RIIalpha SubunitIBA 01/01/2015 - "Serum 25(OH)D and SNPs (n = 960) related to genes with ... cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [ ... cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [ ... cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [ ...
more infohttp://www.curehunter.com/public/keywordSummaryD016115.do

Gene Report for G00001423 - Genes2Cognition Neuroscience Research ProgrammeGene Report for G00001423 - Genes2Cognition Neuroscience Research Programme

Here we found that MTG8 interacted with the regulatory subunit of type II cyclic AMP-dependent protein kinase (PKA RIIalpha). ... Phosphorylation of the type-II regulatory subunit of cyclic-AMP-dependent protein kinase by glycogen synthase kinase 3 and ... Localization of cyclic AMP (cAMP)-dependent protein kinase (PKA) by A kinase-anchoring proteins (AKAPs) restricts the action of ... subunits of cyclic AMP-dependent protein kinase, particularly the RII subunits in rat tissues (Jahnsen, T., Lohmann, S. M., ...
more infohttp://www.genes2cognition.org/db/Gene/G00001423

Bjørn Steen Skålhegg
       - Institutt for medisinske basalfagBjørn Steen Skålhegg - Institutt for medisinske basalfag

Cyclic AMP (cAMP) and cAMP-dependent protein kinase (PKA) are critical regulators of neuronal differentiation. The expression, ... consisting of the regulatory subunit RIalpha and the catalytic subunit Calpha. Low levels of PKA type II consisting of RIIalpha ... Hansson, Vidar; Skålhegg, Bjørn Steen & Tasken, Kjetil (1999). Cyclic-AMP-dependent protein kinase (PKA) in testicular cells. ... LH and FSH regulate via cyclic adenosine 35 cyclic monophosphate (cAMP) and cAMP-dependent protein kinase (PKA), steroid ...
more infohttps://www.med.uio.no/imb/personer/vit/bjoerns/index.html

Molecular basis of AKAP specificity for PKA regulatory subunits. | PsychologyMolecular basis of AKAP specificity for PKA regulatory subunits. | Psychology

Localization of cyclic AMP (cAMP)-dependent protein kinase (PKA) by A kinase-anchoring proteins (AKAPs) restricts the action of ... The high-resolution crystal structures of the docking and dimerization (D/D) domain of the RIIalpha regulatory subunit of PKA ... Molecular basis of AKAP specificity for PKA regulatory subunits. Share this page: ... whereas polar residues are important in conferring R subunit isoform specificity. Using a peptide screening approach, we have ...
more infohttps://psychology.as.uky.edu/molecular-basis-akap-specificity-pka-regulatory-subunits

PRKAR2A - WikipediaPRKAR2A - Wikipedia

... type-II regulatory subunit of cyclic-AMP-dependent protein kinase by glycogen synthase kinase 3 and glycogen synthase kinase 5 ... and characterization of subunits of cAMP-dependent protein kinase in human testis. Reverse mobilities of human RII alpha and ... "MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". ... "Ezrin is a cyclic AMP-dependent protein kinase anchoring protein". The EMBO Journal. 16 (1): 35-43. doi:10.1093/emboj/16.1.35. ...
more infohttps://en.wikipedia.org/wiki/PRKAR2A

cGMP BIOLOG Life Science InstitutecGMP BIOLOG Life Science Institute

Target receptors for the second messenger cyclic GMP include protein kinase G isozymes, cGMP-gated ion channels as well as cGMP ... as a Potent and Specific Activator of cyclic AMP- dependent Protein Kinase in Cell Extracts and Intact Cells" ... J. Biochem., 268, 6197 - 6206 (2001), "The Regulatory Subunit of a cGMP- regulated Protein Kinase A of Trypanosoma Brucei" ... Pharmacol., 387, 1163 - 1175 (2014), "N4-monobutyryl-cCMP Activates PKA RIalpha and PKA RIIalpha more Potently and with Higher ...
more infohttps://www.biolog.de/cgmp

AKAP5 Gene - GeneCards | AKAP5 Protein | AKAP5 AntibodyAKAP5 Gene - GeneCards | AKAP5 Protein | AKAP5 Antibody

Protein Coding), A-Kinase Anchoring Protein 5, including: function, proteins, disorders, pathways, orthologs, and expression. ... Binding protein for dimer of the RII-beta regulatory subunit of cAMP-dependent protein kinase (PKA) and also for the protein ... RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a ... cyclic amp. Experimental. *MalaCards. *Medline Plus. Pharma. 0. (2) Additional Compounds for AKAP5 Gene - From: Novoseek ...
more infohttps://www.genecards.org/cgi-bin/carddisp.pl?gene=AKAP5

Signal transduction PKA signalingSignal transduction PKA signaling

Biological Actions of Activated RSK1 Are Determined by Its Interactions with Subunits of Cyclic AMP-Dependent Protein Kinase. ... Regulation of anchoring of the RIIalpha regulatory subunit of PKA to AKAP95 by threonine phosphorylation of RIIalpha: ... A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent ... PKA-cat may be regulated by 3-phosphoinositide dependent protein kinase-1 ( PDK-1 ) [15], Protein kinase (cAMP-dependent, ...
more infohttp://pathwaymaps.com/maps/675/

Frontiers | Candidate genes in ocular dominance plasticity | NeuroscienceFrontiers | Candidate genes in ocular dominance plasticity | Neuroscience

... acetylcholine esterase and the catalytic subunit of cAMP-dependent protein kinase A. This was indicative of the viability of ... The list contained unproven, but not surprising, candidates, such as the genes for IGF-1, NCAM1, NOGO-A, the gamma2 subunit of ... The list contained unproven, but not surprising, candidates, such as the genes for IGF-1, NCAM1, NOGO-A, the gamma2 subunit of ... The objective of this study was to identify new candidate genes involved in experience-dependent plasticity. To this aim, we ...
more infohttps://www.frontiersin.org/articles/10.3389/fnins.2012.00011/full

Drug-induced Parkinsons disease modulates protein kinase A and Olfactory Marker Protein in the mouse olfactory bulb |...Drug-induced Parkinson's disease modulates protein kinase A and Olfactory Marker Protein in the mouse olfactory bulb |...

Olfactory Marker Protein decreased in the olfactory bulb of MPTP mice, while a cyclic AMP-dependent protein kinase increased in ... Differential expression and Ser 897 phosphorylation of striatal N-methyl-d-aspartate receptor subunit NR1 in animal models of ... murine PKA RIIalpha (Santa Cruz Biotechnology, Heidelberg, Germany, 1:200); adjacent sections were incubated with 100 nM 8- ... Olfactory Marker Protein and cyclic AMP-dependent protein kinase as an intracellular pathway involved in dopaminergic ...
more infohttps://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/s12993-017-0119-2

Sp-cAMPS, triethyl ammonium salt BIOLOG Life Science InstituteSp-cAMPS, triethyl ammonium salt BIOLOG Life Science Institute

... cyclic AMP agonist). Considerably higher resistance against cyclic nucleotide phosphodiesterases compared to dibutyryl- or 8-Br ... "Crystal Structures of RI Alpha Subunit of Cyclic Adenosine 5 monophosphate (cAMP)-dependent Protein Kinase Complexed with (R-p ... Pharmacol., 387, 1163 - 1175 (2014), "N4-monobutyryl-cCMP Activates PKA RIalpha and PKA RIIalpha more Potently and with Higher ... Cyclic Nucleotide Protein Phosphorylation Res., 10, 371 - 382 (1985), "Inhibition of Cyclic AMP- Dependent Protein Kinase ...
more infohttps://www.biolog.de/sp-camps-3365

Protein ks | Article about protein ks by The Free DictionaryProtein k's | Article about protein k's by The Free Dictionary

Find out information about protein ks. Any enzyme that catalyzes phosphorylation reactions Explanation of protein ks ... cyclic AMP-dependent protein kinase. *Cyclic Nucleotides. *cyclin-dependent kinase. *cyclin-dependent kinase activating kinase ... protein kinase A RII-alpha subunit. *protein kinase A type-1a regulatory subunit ... kinase. (redirected from protein ks). Also found in: Dictionary, Thesaurus, Medical. kinase. [′kī‚nās] (biochemistry) Any ...
more infohttps://encyclopedia2.thefreedictionary.com/protein+k

Pain modulators regulate the dynamics of PKA-RII phosphorylation in subgroups of sensory neurons | Journal of Cell SciencePain modulators regulate the dynamics of PKA-RII phosphorylation in subgroups of sensory neurons | Journal of Cell Science

1999). PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase regulated by the regulatory subunit type I. J. ... the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A ... 2004). Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII ... Protein kinase A (PKA) represents a family of tetrameric kinases composed of regulatory (R) and catalytic (C) subunits. At low ...
more infohttp://jcs.biologists.org/content/127/1/216

Mouse | Neuroinflammation - Canopy BioSciencesMouse | Neuroinflammation - Canopy BioSciences

... cyclic AMP responsive element binding protein.cyclic nucleotide phosphodiesterase 1.cyclin dependent kinase inhibitor. ... voltage-dependent calcium channel gamma subunit-like protein.VPF.VPP2.W.W117m.W91664.wa-1.wa-2.wa1.wa2.Wa5.WAF1.WASP.waved 1. ... ribosomal protein L43.Ric.RICK.rickettsia tsutsugamushi resistance.RIG-I.RII(alpha).RII(beta).RIKEN cDNA 0610010I06 gene.RIKEN ... protamine RNA binding protein.protein kinase.protein kinase C substrate.protein S.protein-glutamine-gamma-glutamyltransferase. ...
more infohttps://canopybiosciences.com/product/neuroinflammation-panel-mouse/
  • During retinoic acid-induced differentiation, the RIalpha and RIIalpha expressions remained in the cytoplasm, while we observed a strong upregulation of RIIbeta, located to the whole cytoplasm including neurite extensions. (uio.no)
  • Induction of Cbeta splice variants and formation of novel forms of protein kinase A type II holoenzymes during retinoic acid-induced differentiation of human NT2 cells. (uio.no)
  • Using a high content screening microscopy approach, we identified the RIIβ subunit of PKA-II to be predominantly expressed in a subgroup of sensory neurons. (biologists.org)
  • Low levels of PKA type II consisting of RIIalpha or RIIbeta associated with Calpha were also detected, mainly in the cytoplasm and in the Golgi-centrosomal area. (uio.no)
  • The expression, levels and activities of PKA subunits were studied prior to and during differentiation of the human neuronal precursor cell line NTera 2 (NT2). (uio.no)