Identification of a multifunctional docking site on the catalytic unit of phosphodiesterase-4 (PDE4) that is utilised by multiple interaction partners
| Autor: | Frank Christian, George S. Baillie, Ruth MacLeod, David R. Adams, Miles D. Houslay, Kirsty F. Houslay |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
cyclic nucleotide phosphodiesterases
0301 basic medicine Amino Acid Motifs SUMO protein Gene Expression Mitogen-activated protein kinase kinase Biochemistry Protein Structure Secondary MAP2K7 protein-protein interaction UBC9 Catalytic Domain Chlorocebus aethiops Cyclic AMP beta-Arrestins Research Articles peptide array Mitogen-Activated Protein Kinase 1 chemistry.chemical_classification Mitogen-Activated Protein Kinase 3 ERK1/2 Kinase Intracellular Signaling Peptides and Proteins Recombinant Proteins Molecular Docking Simulation protein kinase A (PKA) Erk src-Family Kinases COS Cells Phosphorylation Microtubule-Associated Proteins Protein Binding Signal Transduction Research Article protein–protein interactions Protein Serine-Threonine Kinases Biology MK2 03 medical and health sciences LYN BETA-ARRESTIN cAMP Animals Humans Phosphodiesterase Protein Interaction Domains and Motifs Protein kinase A Molecular Biology PAFAH1B1 DNA ligase MAPKAPK2 Cell Biology Cyclic AMP-Dependent Protein Kinases Cyclic Nucleotide Phosphodiesterases Type 4 Lis1 HEK293 Cells 030104 developmental biology chemistry 1-Alkyl-2-acetylglycerophosphocholine Esterase Ubiquitin-Conjugating Enzymes PDE4 |
| Zdroj: | Biochemical Journal Houslay, K, Christian, F, MacLeod, R, Adams, D, Houslay, M D & Baillie, G S 2017, ' Identification of a multifunctional docking site on the catalytic unit of phosphodiesterase-4 (PDE4) that is utilised by multiple interaction partners ', Biochemical Journal, vol. 474, no. 4, pp. 597-609 . https://doi.org/10.1042/BCJ20160849 |
| ISSN: | 0264-6021 |
| Popis: | Cyclic AMP (cAMP)-specific phosphodiesterase-4 (PDE4) enzymes underpin compartmentalised cAMP signalling by localising to distinct signalling complexes. PDE4 long isoforms can be phosphorylated by mitogen-activated protein kinase-activated protein kinase 2 (MK2), which attenuates activation of such enzymes through their phosphorylation by protein kinase A. Here we show that MK2 interacts directly with PDE4 long isoforms and define the sites of interaction. One is a unique site that locates within the regulatory upstream conserved region 1 (UCR1) domain and contains a core Phe141, Leu142 and Tyr143 (FLY) cluster (PDE4A5 numbering). Located with the second site is a critical core Phe693, Glu694, Phe695 (FQF) motif that is also employed in the sequestering of PDE4 long forms by an array of other signalling proteins, including the signalling scaffold β-arrestin, the tyrosyl kinase Lyn, the SUMOylation E2 ligase UBC9, the dynein regulator Lis1 (PAFAH1B1) and the protein kinase Erk. We propose that the FQF motif lies at the heart of a multifunctional docking (MFD) site located within the PDE4 catalytic unit. It is clear from our data that, as well as aiding fidelity of interaction, the MFD site confers exclusivity of binding between PDE4 and a single specific partner protein from the cohort of signalling proteins whose interaction with PDE4 involves the FQF motif. |
| Databáze: | OpenAIRE |
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