Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding

Herberg, Friedrich W.; Maleszka, Ariane; Eide, T. J.; Vossebein, Lutz; Taskén, Kjetil

doi:10.1006/jmbi.2000.3662

Cited by 180 publications

(180 citation statements)

References 44 publications

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“…However, the native RI binding affinities of AKAP79 and AKAP-Lbc are 500-fold less for RI than for RII. This difference suggests that these AKAPs will preferentially associate with the type II PKA inside cells when both kinase subtypes are available (40,53). Likewise, AKAP-IS exhibits a 500-fold preference for RII over RI in vitro, and its interaction with RI cannot be detected inside cells.…”

Section: Discussionmentioning

confidence: 99%

“…Structural studies on two such AKAP peptides indicate that this region folds to form an amphipathic helix that slots into a binding pocket formed by the amino-terminal regions of each RII protomer (36,37). Nonetheless, individual AKAPs bind RII with dissociation constants (K d ) ranging from 2 to 90 nM, which ref lects the diversity of sequences that form these PKAanchoring regions (18,(38)(39)(40). Therefore, we initiated a comprehensive analysis of multiple AKAP sequences in an attempt to define a consensus PKA-anchoring motif.…”

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confidence: 99%

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Bioinformatic design of A-kinase anchoring protein- in silico : A potent and selective peptide antagonist of type II protein kinase A anchoring

Alto

Soderling

Hoshi

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

153

144

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Compartmentalization of the cAMP-dependent protein kinase (PKA) is coordinated through association with A-kinase anchoring proteins (AKAPs). A defining characteristic of most AKAPs is a 14-to 18-aa sequence that binds to the regulatory subunits (RI or RII) of the kinase. Cellular delivery of peptides to these regions disrupts PKA anchoring and has been used to delineate a physiological role for AKAPs in the facilitation of certain cAMP-responsive events. Here, we describe a bioinformatic approach that yields an RIIselective peptide, called AKAP-in silico (AKAP-IS), that binds RII with a Kd of 0.4 nM and binds RI with a Kd of 277 nM. AKAP-IS associates with the type II PKA holoenzyme inside cells and displaces the kinase from natural anchoring sites. Electrophysiological recordings indicate that perfusion of AKAP-IS evokes a more rapid and complete attenuation of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor currents than previously described anchoring inhibitor peptides. Thus, computerbased and peptide array screening approaches have generated a reagent that binds PKA with higher affinity than previously described AKAPs.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bioinformatic design of A-kinase anchoring protein- in silico : A potent and selective peptide antagonist of type II protein kinase A anchoring

Alto

Soderling

Hoshi

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

153

144

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“…Fusion proteins containing an AD or DDD and intact RII subunits have been expressed recombinantly in E. coli with good yield (24). Thus, it does not appear that the choice of expression systems for an A or B component will be restricted by the DDD or AD group, respectively.…”

Section: Discussionmentioning

confidence: 99%

Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting

Rossi

Goldenberg

Cardillo

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

192

206

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We describe a platform technology, termed the dock and lock method, which uses a natural binding between the regulatory subunits of cAMP-dependent protein kinase and the anchoring domains of A kinase anchor proteins for general application in constructing bioactive conjugates of different protein and nonprotein molecules from modular subunits on demand. This approach could allow quantitative and site-specific coupling of many different biological substances for diverse medical applications. The dock and lock method is validated herein by producing bispecific, trivalent-binding complexes composed of three stably linked Fab fragments capable of selective delivery of radiotracers to human cancer xenografts, resulting in rapid, significantly improved cancer targeting and imaging, providing tumor͞blood ratios from 66 ؎ 5 at 1 h to 395 ؎ 26 at 24 h. bispecific antibody ͉ fusion proteins ͉ A kinase ͉ protein engineering ͉ site-specific conjugation

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“…These sequences are amphipathic helices that provide a hydrophobic pocket for the binding of PKA R-subunit dimers [13,53]. The affinity of the R subunits for binding to these regions is in the nanomolar range: 0.5 nM for RI and 4.5 nM for RII [54].This sequence provides a basis for the Ht-31 blocking peptide (residues 493-515) [4], which has been shown to block the interaction of the β 2 AR with AKAP79 [47] and AKAP250 [19].…”

Section: Pka Ri/ii Binding Domainmentioning

confidence: 99%

AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes

Malbon

Tao

Wang

2004

Biochemical Journal

100

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Cell signalling mediated via GPCRs (G-protein-coupled receptors) is a major paradigm in biology, involving the assembly of receptors, G-proteins, effectors and downstream elements into complexes that approach in design 'solid-state' signalling devices. Scaffold molecules, such as the AKAPs (A-kinase anchoring proteins), were discovered more than a decade ago and represent dynamic platforms, enabling multivalent signalling. AKAP79 and AKAP250 were the first to be shown to bind to membrane-embedded GPCRs, orchestrating the interactions of various protein kinases (including tyrosine kinases), protein phosphatases (e.g. calcineurin) and cytoskeletal elements with at least one member of the superfamily of GPCRs, the prototypical β 2 -adrenergic receptor. In this review, the multivalent interactions of AKAP250 with the cell membrane, receptor, cytoskeleton and constituent components are detailed, providing a working model for AKAP-based GPCR signalling complexes. Dynamic regulation of the AKAP-receptor complex is mediated by ordered protein phosphorylation.

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Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding

Cited by 180 publications

References 44 publications

Bioinformatic design of A-kinase anchoring protein- in silico : A potent and selective peptide antagonist of type II protein kinase A anchoring

Bioinformatic design of A-kinase anchoring protein- in silico : A potent and selective peptide antagonist of type II protein kinase A anchoring

Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting

AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes

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