Towards Dissecting the Mechanism of Protein Phosphatase‐1 Inhibition by Its C‐Terminal Phosphorylation
Copyright policy )Towards Dissecting the Mechanism of Protein Phosphatase‐1 Inhibition by Its C‐Terminal Phosphorylation
AbstractPhosphoprotein phosphatase‐1 (PP1) is a key player in the regulation of phospho‐serine (pSer) and phospho‐threonine (pThr) dephosphorylation and is involved in a large fraction of cellular signaling pathways. Aberrant activity of PP1 has been linked to many diseases, including cancer and heart failure. Besides a well‐established activity control by regulatory proteins, an inhibitory function for phosphorylation (p) of a Thr residue in the C‐terminal intrinsically disordered tail of PP1 has been demonstrated. The associated phenotype of cell‐cycle arrest was repeatedly proposed to be due to autoinhibition of PP1 through either conformational changes or substrate competition. Here, we use PP1 variants created by mutations and protein semisynthesis to differentiate between these hypotheses. Our data support the hypothesis that pThr exerts its inhibitory function by mediating protein complex formation rather than by a direct mechanism of structural changes or substrate competition.
- KU Leuven Belgium
- EUROPEAN MOLECULAR BIOLOGY LABORATORY Germany
- University of Geneva Switzerland
- University of Freiburg Germany
- Katholieke Universiteit Leuven Belgium
Threonine, 570, Biochemistry & Molecular Biology, MITOTIC EXIT, 3101 Biochemistry and cell biology, Protein Conformation, Chemistry, Medicinal, 0601 Biochemistry and Cell Biology, Protein Domains, Protein Phosphatase 1, Serine, biomimetic synthesis, Humans, Pharmacology & Pharmacy, Phosphorylation, 3404 Medicinal and biomolecular chemistry, protein phosphatase-1 (PP1) regulation, Science & Technology, ARREST, 0304 Medicinal and Biomolecular Chemistry, phosphorylation, Organic Chemistry, Intracellular Signaling Peptides and Proteins, PP1, DEPHOSPHORYLATION, Protein phosphatase-1 (PP1) regulation, Communications, ALPHA, Biomimetic synthesis, peptides, Peptides, Life Sciences & Biomedicine, protein semisynthesis, Protein semisynthesis, Protein Binding
Threonine, 570, Biochemistry & Molecular Biology, MITOTIC EXIT, 3101 Biochemistry and cell biology, Protein Conformation, Chemistry, Medicinal, 0601 Biochemistry and Cell Biology, Protein Domains, Protein Phosphatase 1, Serine, biomimetic synthesis, Humans, Pharmacology & Pharmacy, Phosphorylation, 3404 Medicinal and biomolecular chemistry, protein phosphatase-1 (PP1) regulation, Science & Technology, ARREST, 0304 Medicinal and Biomolecular Chemistry, phosphorylation, Organic Chemistry, Intracellular Signaling Peptides and Proteins, PP1, DEPHOSPHORYLATION, Protein phosphatase-1 (PP1) regulation, Communications, ALPHA, Biomimetic synthesis, peptides, Peptides, Life Sciences & Biomedicine, protein semisynthesis, Protein semisynthesis, Protein Binding
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