Adaptors and integrators

Cowburn, David

doi:10.1016/s0969-2126(96)00106-2

Cited by 19 publications

(9 citation statements)

References 20 publications

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“…It is becoming increasingly clear that PDZ motifs are well‐tailored to bind to the carboxy‐termini of proteins [15, 17, 20, 32, 33]. Use of the oriented peptide library technique has resulted in a catalogue of unique optimal sequences for multiple individual PDZ motifs, defined primarily by the carboxyl terminal three to seven residues of the target peptide [34].…”

Section: Discussionmentioning

confidence: 99%

The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV^* carboxyterminal sequences

et al. 1997

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PDZ motifs are small protein-protein interaction modules that are thought to play a role in the clustering of submembranous signalling molecules. The specificity and functional consequences of their associative actions is still largely unknown. Using two-hybrid methodology we here demonstrate that the PDZ motif of neuronal nitric oxide synthase (nNOS) can mediate the binding to several other proteins in brain. Peptide library screening showed that proteins bearing a carboxy-terminal G(D,E)XV* sequence are preferred targets for the nNOS amino-terminal PDZ motif. Potential nNOS targets include a melanoma-associated antigen, cyclophilins and the alC-adrenergic receptor.

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Section: Discussionmentioning

confidence: 99%

The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV^* carboxyterminal sequences

et al. 1997

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“…The PDZ domain has an overall structure very much like the phosphotyrosine binding domain, even though they are unrelated in function (17,18). Essentially, it is a globular domain formed by six ␤ strands (designated ␤A-␤F) and two ␣ helices (designated ␣A and ␣B) arranged into an up-and-down ␤-barrel (14, 15).…”

Section: Pdzmentioning

confidence: 99%

Cyclic Peptides as Non-carboxyl-terminal Ligands of Syntrophin PDZ Domains

Gee¹,

Sekely²,

Lombardo³

et al. 1998

Journal of Biological Chemistry

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Syntrophins, a family of intracellular peripheral membrane proteins of the dystrophin-associated protein complex (DAPC), each contain a single PDZ domain. Syntrophin PDZ domains bind C-terminal peptide sequences with the consensus R/K-E-S/T-X-V-COOH, an interaction that mediates association of skeletal muscle sodium channels with the DAPC. Here, we have isolated cyclic peptide ligands for syntrophin PDZ domains from a library of combinatorial peptides displayed at the N terminus of protein III of bacteriophage M13. Affinity selection from a library of X 10 C peptides yielded ligands with the consensus X-(R/K)-E-T-C-L/M-A-G-X-⌿-C, where ⌿ represents any hydrophobic amino acid. These peptides contain residues (underlined) similar to the C-terminal consensus sequence for binding to syntrophin PDZ domains and bind to the same site on syntrophin PDZ domains as C-terminal peptides, but do not bind to other closely related PDZ domains. PDZ binding is dependent on the formation of an intramolecular disulfide bond in the peptides, since treatment with dithiothreitol, or substitution of either of the two cysteines with alanines, eliminated this activity. Furthermore, amino acid replacements revealed that most residues in the phage-selected peptides are required for binding. Our results define a new mode of binding to PDZ domains and suggest that proteins containing similar conformationally constrained sequences may be ligands for PDZ domains. PDZ1 domains are 80 -90-amino acid modules present in numerous eukaryotic proteins. They were first described as a series of three internal, repeated elements within the postsynaptic density (PSD)-95 protein (1). In fact, the name PDZ is derived from three proteins first recognized to contain repeats of this domain: PSD-95; the Drosophila discs-large tumor suppressor protein, Dlg; and the mammalian tight-junction protein zona occludens-1, ZO-1 (2-5). PDZ domains have since been identified in a large number of multifunctional proteins, many of which are associated with specialized regions of cell to cell contact such as tight junctions, septate junctions, and synaptic junctions (6). The PDZ domain may be an evolutionarily old domain, as it has been detected in mammalian, nematode, yeast, plant, and bacterial genomic sequences by computer analysis (7).PDZ domains mediate protein-protein interactions by at least two distinct mechanisms. Certain PDZ domains bind directly to specific recognition sequences at the C terminus of transmembrane proteins. For example, the second PDZ domain of PSD-95 interacts with an S/T-X-V-COOH motif in N-methyl-D-aspartate receptor 2B subunits (8, 9) and in Shaker-type potassium channels (10). PDZ domains can also form heterotypic dimers with other PDZ domains. For instance, the Nterminal region of nNOS, which itself contains a PDZ domain, binds directly to PDZ domains in both PSD-95 and ␣ 1 -syntrophin, a component of the dystrophin-associated protein complex (DAPC) (11). A third possible mode of interaction, in which the consensus binding sequence is locat...

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“…Several diverse protein domains which regulate the formation of such complexes have been identified and characterized. (1)(2)(3)(4) This article focuses on signal transduction events regulated by intracellular effectors pos-sessing association motifs known as src homology 2 (SH2) and src homology 3 (SH3) domains.…”

Section: Introductionmentioning

confidence: 99%

The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events

McCarty

1998

Bioessays

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The process generally termed signal transduction involves the coordinated relay of information from extracellular cues to intracellular effectors, subsequently leading to a specified cellular response. The formation of multimeric protein complexes is a critical step in the activation of most intracellular signal transduction cascades. In many cases, these processes are initiated by a family of molecules consisting of protein association motifs known as src homology 2 and 3 (SH2 and SH3) domains. This review focuses on a group of proteins within this family that lack intrinsic enzymatic functions and consist almost entirely of SH2 and SH3 domains. Termed “adaptors,” these proteins serve to physically bridge activated cell surface receptors to various intracellular signal transduction pathways. Here, I briefly summarize current knowledge concerning the various adaptor proteins and place a particular emphasis on Nck. Various data are discussed which collectively support a role for Nck in the regulation of multiple intracellular signaling events. BioEssays 20:913–921, 1998. © 1998 John Wiley & Sons, Inc.

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Adaptors and integrators

Abstract: The PTB domain expands both the PH-domain set and peptide-protein recognition motifs; the PDZ domain shows an intriguing resemblance.

Cited by 19 publications

References 20 publications

The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV^* carboxyterminal sequences

The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV^* carboxyterminal sequences

Cyclic Peptides as Non-carboxyl-terminal Ligands of Syntrophin PDZ Domains

The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events

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Adaptors and integrators

Abstract: The PTB domain expands both the PH-domain set and peptide-protein recognition motifs; the PDZ domain shows an intriguing resemblance.

Cited by 19 publications

References 20 publications

The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV* carboxyterminal sequences

The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV* carboxyterminal sequences

Cyclic Peptides as Non-carboxyl-terminal Ligands of Syntrophin PDZ Domains

The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events

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The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV^* carboxyterminal sequences

The neuronal nitric oxide synthase PDZ motif binds to ‐G(D,E)XV^* carboxyterminal sequences