The brain of the cell

Marks, Friedrich

doi:10.1002/9783527615032.ch1

Cited by 4 publications

(1 citation statement)

References 156 publications

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“…Therefore, it is a crucial challenge to decipher the factors that may influence the balance between the soluble, "normal," protein and its pathogenic form, by either preventing or triggering multimerization. Bearing in mind that about one-third of mammalian proteins contain covalently bound phosphate and that the possibility that such a reversible phosphorylation is responsible for the control of nearly all aspects of cell life (28), the possibility that α-syn might also undergo this kind of covalent modification has been studied in several laboratories. Previous investigations have shown that α-syn can be Ser-phosphorylated by protein kinases CK1 and CK2 at a residue (Ser-129) whose phosphorylation could be also observed in vivo if Ser/Thr protein phosphatases were inhibited by okadaic acid (29,30).…”

Section: Discussionmentioning

confidence: 99%

Multiple phosphorylation of α‐synuclein by protein tyrosine kinase Syk prevents eosin‐induced aggregation

et al. 2001

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The presence of aggregated alpha-synuclein molecules is a common denominator in a variety of neurodegenerative disorders. Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (Syk), which phosphorylates three tyrosyl residues in its C-terminal domain (Y-125, Y-133, and Y-136), as revealed from experiments with mutants where these residues have been individually or multiply replaced by phenylalanine. In contrast, only Y-125 is phosphorylated by Lyn and c-Fgr. Eosin-induced multimerization is observed with wild-type alpha-syn, either phosphorylated or not by Lyn, and with all its Tyr to Phe mutants but not with the protein previously phosphorylated by Syk. Syk-mediated phosphorylation also counteracts alpha-syn assembly into filaments as judged from the disappearance of alpha-syn precipitated upon centrifugation at 100,000 x g. We also show that Syk and alpha-syn colocalize in the brain, and upon cotransfection in Chinese hamster ovary cells, alpha-syn becomes Tyr-phosphorylated by Syk. Moreover, Syk and alpha-syn interact with each other as judged from the mammalian two-hybrid system approach. These data suggest that Syk or tyrosine kinase(s) with similar specificity may play an antineurodegenerative role by phosphorylating a-syn, thereby preventing its aggregation.

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Section: Discussionmentioning

confidence: 99%

Multiple phosphorylation of α‐synuclein by protein tyrosine kinase Syk prevents eosin‐induced aggregation

et al. 2001

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The serine, threonine, and/or tyrosine-specific protein kinases and protein phosphatases of prokaryotic organisms: a family portrait

1998

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Inspection of the genomes for the bacteria Bacillus subtilis 168, Borrelia burgdorferi B31, Escherichia coli K-12, Haemophilus influenzae KW20, Helicobacter pylori 26695, Mycoplasma genitalium G-37, and Synechocystis sp PCC 6803 and for the archaeons Archaeoglobus fulgidus VC-16 DSM4304, Methanobacterium thermoautotrophicum delta H, and Methanococcus jannaschii DSM2661 revealed that each contains at least one ORF whose predicted product displays sequence features characteristic of eukaryote-like protein-serine/threonine/tyrosine kinases and protein-serine/threonine/tyrosine phosphatases. Orthologs for all four major protein phosphatase families (PPP, PPM, conventional PTP, and low molecular weight PTP) were present in the bacteria surveyed, but not all strains contained all types. The three archaeons surveyed lacked recognizable homologs of the PPM family of eukaryotic protein-serine/threonine phosphatases; and only two prokaryotes were found to contain ORFs for potential phosphatases from all four major families. Intriguingly, our searches revealed a potential ancestral link between the catalytic subunits of microbial arsenate reductases and the protein-tyrosine phosphatases; they share similar ligands (arsenate versus phosphate) and features of their catalytic mechanism (formation of arseno-versus phospho-cysteinyl intermediates). It appears that all prokaryotic organisms, at one time, contained the genetic information necessary to construct protein phosphorylation-dephosphorylation networks that target serine, threonine, and/or tyrosine residues on proteins. However, the potential for functional redundancy among the four protein phosphatase families has led many prokaryotic organisms to discard one, two, or three of the four.

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Biochemical Activities of Minute Virus of Mice Nonstructural Protein NS1 Are Modulated In Vitro by the Phosphorylation State of the Polypeptide

Nüesch

Corbau

Tattersall

et al. 1998

J Virol

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NS1, the 83-kDa major nonstructural protein of minute virus of mice (MVM), is a multifunctional nuclear phosphoprotein which is required in a variety of steps during progeny virus production, early as well as late during infection. NS1 is the initiator protein for viral DNA replication. It binds specifically to target DNA motifs; has site-specific single-strand nickase, intrinsic ATPase, and helicase activities; trans regulates viral and cellular promoters; and exerts cytotoxic stress on the host cell. To investigate whether these multiple activities of NS1 depend on posttranslational modifications, in particular phosphorylation, we expressed His-tagged NS1 in HeLa cells by using recombinant vaccinia viruses, dephosphorylated it at serine and threonine residues with calf intestine alkaline phosphatase, and compared the biochemical activities of the purified un(der)phosphorylated (NS1O) and the native (NS1P) polypeptides. Biochemical analyses of replicative functions of NS1O revealed a severe reduction of intrinsic helicase activity and, to a minor extent, of ATPase and nickase activities, whereas its affinity for the target DNA sequence [ACCA]2–3 was enhanced compared to that of NS1P. In the presence of endogenous protein kinases found in replication extracts, NS1O showed all functions necessary for resolution and replication of the 3′ dimer bridge, indicating reactivation of NS1O by rephosphorylation. Partial reactivation of the helicase activity was found as well when NS1O was incubated with protein kinase C.

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The brain of the cell

Cited by 4 publications

References 156 publications

Multiple phosphorylation of α‐synuclein by protein tyrosine kinase Syk prevents eosin‐induced aggregation

Multiple phosphorylation of α‐synuclein by protein tyrosine kinase Syk prevents eosin‐induced aggregation

The serine, threonine, and/or tyrosine-specific protein kinases and protein phosphatases of prokaryotic organisms: a family portrait

Biochemical Activities of Minute Virus of Mice Nonstructural Protein NS1 Are Modulated In Vitro by the Phosphorylation State of the Polypeptide

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