Protein phosphatase 1 catalytic isoforms: specificity toward interacting proteins.

The coordinated and reciprocal action of serine-threonine protein kinases and protein phosphatases produces transitory phosphorylation, a fundamental regulatory mechanism for many biological processes. Phosphoprotein phosphatase 1 (PPP1), a major serine-threonine phosphatase, in particular, is ubiquitously distributed and regulates a broad range of cellular functions, including glycogen metabolism, cell cycle progression, and muscle relaxation. PPP1 has evolved effective catalytic machinery but in vitro lacks substrate specificity.

Synphilin-1A is a phosphoprotein phosphatase 1-interacting protein and affects PPP1 sorting to subcellular compartments.

Lewy bodies (LBs) are synphilin-1 (Sph1)-containing aggregates and histological hallmarks of Parkinson's disease. Therefore, understanding processes which modulate the aggregation of Sph1, or its isoform Sph1A, will contribute to our understanding of LBs formation. Protein phosphorylation promotes aggregation, but protein phosphatases with activity towards Sph1 have not been described.

An intriguing shift occurs in the novel protein phosphatase 1 binding partner, TCTEX1D4: evidence of positive selection in a pika model.

T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) contains the canonical phosphoprotein phosphatase 1 (PPP1) binding motif, composed by the amino acid sequence RVSF. We identified and validated the binding of TCTEX1D4 to PPP1 and demonstrated that indeed this protein is a novel PPP1 interacting protein. Analyses of twenty-one mammalian species available in public databases and seven Lagomorpha sequences obtained in this work showed that the PPP1 binding motif 90RVSF93 is present in all of them and is flanked by a palindromic sequence, PLGS, except in three species of pikas (Ochotona princeps, O.

TCTEX1D4, a novel protein phosphatase 1 interactor: connecting the phosphatase to the microtubule network.

Reversible phosphorylation plays an important role as a mechanism of intracellular control in eukaryotes. PPP1, a major eukaryotic Ser/Thr-protein phosphatase, acquires its specificity by interacting with different protein regulators, also known as PPP1 interacting proteins (PIPs). In the present work we characterized a physiologically relevant PIP in testis.

Identification of a novel complex AβPP:Fe65:PP1 that regulates AβPP Thr668 phosphorylation levels.

The amyloid-β protein precursor (AβPP) binds several proteins determining metabolism, processing, and the physiological fate of the former. Among these is Fe65, a protein with specific functional significance for AβPP, in particular conferring stability when the latter is dephosphorylated on Thr668. Thus, it follows that phosphatases like protein phosphatase 1 (PP1) are relevant to AβPP processing.

Protein phosphatase 1γ isoforms linked interactions in the brain.

Posttranslational protein modifications, in particular reversible protein phosphorylation, are important regulatory mechanisms involved in cellular signaling transduction pathways. Thousands of human proteins are phosphorylatable and the tight regulation of phosphorylation states is crucial for cell maintenance and development. Protein phosphorylation occurs primarily on serine, threonine, and tyrosine residues, through the antagonistic actions of protein kinases and phosphatases.

Protein phosphatase 1α interacting proteins in the human brain.

Protein Phosphatase 1 (PP1) is a major serine/threonine-phosphatase whose activity is dependent on its binding to regulatory subunits known as PP1 interacting proteins (PIPs), responsible for targeting PP1 to a specific cellular location, specifying its substrate or regulating its action. Today, more than 200 PIPs have been described involving PP1 in panoply of cellular mechanisms. Moreover, several PIPs have been identified that are tissue and event specific.

Identification of the human testis protein phosphatase 1 interactome.

Protein phosphorylation is a critical regulatory mechanism in cellular signalling. To this end, PP1 is a major eukaryotic serine/threonine-specific phosphatase whose cellular functions, in turn, depend on complexes it forms with PP1 interacting proteins-PIPs. The importance of the testis/sperm-enriched variant, PP1γ2, in sperm motility and spermatogenesis has previously been shown.

Protein phosphatase 1 complexes modulate sperm motility and present novel targets for male infertility.

Infertility is a growing concern in modern society, with 30% of cases being due to male factors, namely reduced sperm concentration, decreased motility and abnormal morphology. Sperm cells are highly compartmentalized, almost devoid of transcription and translation consequently processes such as protein phosphorylation provide a key general mechanism for regulating vital cellular functions, more so than for undifferentiated cells. Reversible protein phosphorylation is the principal mechanism regulating most physiological processes in eukaryotic cells.