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C Persson

Publications and source records attributed to C Persson.

At least 37 records · Page 2Linked to original sources

Role of immunoglobulin-like domains 2-4 of the platelet-derived growth factor alpha-receptor in ligand-receptor complex assembly.

Platelet-derived growth factor (PDGF) is a dimeric protein that exerts its effects through tyrosine kinase alpha- and beta-receptors. The extracellular part of each receptor is composed of five Ig-like domains. Recombinant forms of alpha-receptor domains 1-4 (alphaRD1-4), 1-3 (alphaRD1-3), and 1 and 2 (alphaRD1-2) were prepared after expression in Chinese hamster ovary cells and were used to study the assembly of soluble ligand-receptor complexes. When incubated with micromolar concentrations of PDGF, both alphaRD1-3 and alphaRD1-4 formed complexes of 1:2 molar composition, i.e. one dimeric PDGF molecule bound two soluble receptors. alphaRD1-3, in contrast to alphaRD1-4, formed detectable 1:1 complexes under conditions of ligand excess. alphaRD1-4 displayed an increased ability to form 1:2 complexes as compared with alphaRD1-3 under conditions of limiting concentrations of ligand. We thus conclude that Ig-like domain 4-mediated receptor-receptor interactions contribute to 1:2 PDGF.alphaRD1-4 complex formation. Since alphaRD1-4 and alphaRD1-3 were equipotent in blocking binding of subnanomolar concentrations of PDGF to cell-surface receptors, we also conclude that this effect is predominantly achieved through formation of Ig-like domain 4-independent 1:1 ligand-receptor complexes. Finally, since alphaRD1-2 bound PDGF-BB with high affinity, whereas PDGF-AA was bound only with low affinity, we conclude that Ig-like domain 3 of the PDGF alpha-receptor contains epitopes of particular importance for PDGF-AA binding and that most of the PDGF-BB-binding epitopes reside in Ig-like domains 1 and 2.

Animals↗

Identification of a tissue- and differentiation stage-specific enhancer of the VpreB1 gene.

The VpreB and lambda 5 genes encode proteins that associate non-covalently to form the so-called surrogate light (SL) chain. The SL chain complexes with the immunoglobulin heavy chain to form the pre-B cell receptor, which plays a critical role in B cell development. Expression of the murine SL genes is regulated at the level of transcription initiation. Here, we show that a VpreB1 enhancer is located within the 356 bp immediately upstream of the coding sequence. Interestingly, this region exhibits 96% identity to the upstream region of VpreB2. Deletion mapping located the enhancer to between positions -214 and -47 (+1 is the 5'-most transcription initiation site). The enhancer is tissue and differentiation stage specific, and is composed of several DNA elements that are important for its activity. We also show that a transcription factor, early B cell factor, binds to two such elements, and that at least one of these sites is involved in determining enhancer activity.

Animals↗

Bidirectional signaling between Yersinia and its target cell.

Preventing the early host immune defense allows pathogenic Yersinia to proliferate in lymphatic tissue. This ability depends on signaling that occurs between the bacteria and the host cells. Following intimate contact with the target cell a signal is generated within the bacterium that results in increased expression of virulence-associated proteins that are subsequently delivered into the infected cell. These proteins, designated Yops, interfere with the host-cell signaling pathways that are normally activated to eliminate infectious agents.

Humans↗

Interview reliability for assessing mental work demands.

This study presented and evaluated an interview method for the analysis of tasks included in a work situation. What mental demands and possibilities do the work tasks give rise to? When was the work more or less automatic? When was use of active knowledge required? When were problem solving and planning needed? The study included an assessment of the interobserver reliability of the interviews with employees from 5 different careers: bus drivers (n = 10), home service workers (n = 32), carpenters (n = 11), farmers (n = 14), and teachers (n = 26). The extent to which this method can be reproduced in studies of different occupations is discussed. The interobserver reliability was good (.75-.82). There is support for the stability and usefulness of the interview for most types of work concerning the 3 categories of mental demands: routine, active knowledge, and problem solving/creativity.

Adult↗

The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions.

Pathogenic Yersinia resist uptake by eukaryotic cells by a mechanism involving the virulence protein YopH, a protein tyrosine phosphatase. We show that p130Cas and FAK are phosphorylated and recruited to peripheral focal complexes during bacterial uptake in HeLa cells. The inactive form of YopH interacts with the tyrosine phosphorylated forms of FAK and p130Cas and co-localizes with these proteins in focal adhesions. On the other hand, the presence of active YopH results in inhibition of uptake, dephosphorylation of p130Cas and FAK, and disruption of peripheral focal complexes. We suggest that p130Cas and FAK are substrates for YopH and that the dephosphorylation of these proteins impairs the uptake of Yersinia pseudotuberculosis into HeLa cells.

Bacterial Outer Membrane Proteins↗

Identification of cross-reactive antigenic target regions for HIV type 1-specific antibody-dependent cellular cytotoxicity.

Monkey-derived hyperimmune antisera against 40 peptides, together representing the entire envelope gp120 of HIV-1LAI, were used to map antibody-dependent cellular cytotoxicity (ADCC) target regions. Four regions corresponding to amino acids 65-126, 152-230, 248-330, and 445-466 were found to contain epitopes inducing ADCC activity not only against HIV-1LAI-infected cells but also against cells infected with HIV-1SF2 and clinical isolates of HIV-1. When comparing seroreactivity to the individual peptides with ADCC titers none of the regions seemed to be dominant. These results thus describe cross-reactive regions involved in the functional immunity against HIV-1 gp120.

Amino Acid Sequence↗

The YopB protein of Yersinia pseudotuberculosis is essential for the translocation of Yop effector proteins across the target cell plasma membrane and displays a contact-dependent membrane disrupting activity.

During infection of cultured epithelial cells, surface-located Yersinia pseudotuberculosis deliver Yop (Yersinia outer protein) virulence factors into the cytoplasm of the target cell. A non-polar yopB mutant strain displays a wild-type phenotype with respect to in vitro Yop regulation and secretion but fails to elicit a cytotoxic response in cultured HeLa cells and is unable to inhibit phagocytosis by macrophage-like J774 cells. Additionally, the yopB mutant strain was avirulent in the mouse model. No YopE or YopH protein were observed within HeLa cells infected with the yopB mutant strain, suggesting that the loss of virulence of the mutant strain was due to its inability to translocate Yop effector proteins through the target cell plasma membrane. Expression of YopB is necessary for Yersinia-induced lysis of sheep erythrocytes. Purified YopB was shown to have membrane disruptive activity in vitro. YopB-dependent haemolytic activity required cell contact between the bacteria and the erythrocytes and could be inhibited by high, but not low, molecular weight carbohydrates. Similarly, expression of YopE reduced haemolytic activity. Therefore, we propose that YopB is essential for the formation of a pore in the target cell membrane that is required for the cell-to-cell transfer of Yop effector proteins.

Animals↗

YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis.

The PTPase YopH of Yersinia is essential to the ability of these bacteria to block phagocytosis. Wild-type Yersinia pseudotuberculosis, but not the yopH mutant strain, resisted phagocytosis by J774 cells. Ingestion of a yopH mutant was dependent on tyrosine kinase activity. Transcomplementation with wild-type yopH restored the anti-phagocytic effect, whereas introduction of the gene encoding the catalytically inactive yopHC403A was without effect. The PTPase inhibitor orthovanadate impaired the anti-phagocytic effect of the wild-type strain, further demonstrating the importance of bacteria-derived PTPase activity for this event. The ability to resist phagocytosis indicates that the effect of the bacterium is immediately exerted when it becomes associated with the phagocyte. Within 30 s after the onset of infection, wild-type Y. pseudotuberculosis caused a YopH-dependent dephosphorylation of phosphotyrosine proteins in J774 cells. Furthermore, interaction of the cells with phagocytosable strains led to a rapid and transient increase in tyrosine phosphorylation of paxillin and some other proteins, an event dependent on the presence of the bacterial surface-located protein invasin. Co-infection with the phagocytosable strain and the wild-type strain abolished the induction of tyrosine phosphorylation. Taken together, the present findings demonstrate an immediate YopH-mediated dephosphorylation of macrophage phosphotyrosine proteins, suggesting that this PTPase acts by preventing early phagocytosis-linked signalling in the phagocyte.

Animals↗

Increased mRNA expression of IL-6, IL-10, TNF-alpha, and perforin in blood mononuclear cells in human HIV infection.

Evidence has been presented for the involvement of various cytokines, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha, in the pathogenesis of human immunodeficiency virus (HIV) infection. Since measured plasma levels may poorly reflect in vivo production of cytokines, we adopted in situ hybridization with cDNA oligonucleotide probes to enumerate blood mononuclear cells (MNCs) expressing mRNA for IL-6, IL-10, TNF-alpha, and perforin. The HIV-infected patients had elevated levels of MNCs expressing mRNA for all four cytokines compared to healthy controls. Numbers of IL-6 mRNA-expressing cells were higher in patients with clinical AIDS than in asymptomatic seropositive patients, and correlated inversely with CD4+ cell counts in blood, reflecting the involvement of IL-6 in later stages of HIV infection. The described approach could be an alternative way to study cytokines in HIV infection.

Acquired Immunodeficiency Syndrome↗