Seng-Lai Tan

article

Data for the crystal structure of APRIL–BAFF–BAFF heterotrimer

Klaus Maskos, Alfred Lammens, Seng-Lai Tan, Henry Hess, more

Data in Brief > 2016 > 6 > C > 438-444

The TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) modulate B cell function by forming homotrimers and heterotrimers. To determine the structure of a heterotrimer of BAFF and APRIL, these ligands were expressed as a single chain protein in HEK 293 cells, purified by affinity and size exclusion chromatographies, and crystallized. Crystals belonging to...

article

Combined Inhibition of Tumor Necrosis Factor α and Interleukin‐17 As a Therapeutic Opportunity in Rheumatoid Arthritis: Development and Characterization of a Novel Bispecific Antibody

Jens A. A. Fischer, Axel J. Hueber, Stacy Wilson, Margarete Galm, more

Arthritis & Rheumatology > 67 > 1 > 51 - 62

ObjectiveRheumatoid arthritis therapies that are based on inhibition of a single cytokine, e.g., tumor necrosis factor α (TNFα) or interleukin‐6 (IL‐6), produce clinically meaningful responses in only about half of the treated patients. This study was undertaken to investigate whether combined inhibition of TNFα and IL‐17 has additive or synergistic effects in the suppression of mesenchymal cell activation...

article

Recent progress and therapeutic perspectives

Seng-Lai Tan, Cheng Liao, Matthew C. Lucas, Christopher Stevenson, more

Pharmacology and Therapeutics > 2013 > 138 > 2 > 294-309

Spleen Tyrosine Kinase (SYK) and Bruton's Tyrosine Kinase (BTK) are non-receptor cytoplasmic tyrosine kinases that are primarily expressed in cells of hematopoietic lineage. Both are key mediators in coupling activated immunoreceptors to downstream signaling events that affect diverse biological functions, from cellular proliferation, differentiation and adhesion to innate and adaptive immune responses...

article

Bruton's Tyrosine Kinase mediates platelet receptor-induced generation of microparticles: A potential mechanism for amplification of inflammatory responses in rheumatoid arthritis synovial joints

Jonathan Hsu, Yajuan Gu, Seng-Lai Tan, Satwant Narula, more

Immunology Letters > 2013 > 150 > 1-2 > 97-104

Platelet microparticles (pMPs) are small membrane-coated vesicles that are released from the plasma membrane upon platelet activation. In the joint fluid of patients with rheumatoid arthritis, pMP can interact with and activate fibroblast-like synoviocytes (FLS), which are important effector cells that mediate both immune activation and joint destruction. The signaling process by which engagement...

article

TBK1 Directly Engages Akt/PKB Survival Signaling to Support Oncogenic Transformation

Yi-Hung Ou, Michael Torres, Rosalyn Ram, Etienne Formstecher, more

Molecular Cell > 2011 > 41 > 4 > 458-470

The innate immune-signaling kinase, TBK1, couples pathogen surveillance to induction of host defense mechanisms. Pathological activation of TBK1 in cancer can overcome programmed cell death cues, enabling cells to survive oncogenic stress. The mechanistic basis of TBK1 prosurvival signaling, however, has been enigmatic. Here, we show that TBK1 directly activates AKT by phosphorylation of the canonical...

article

Phosphorylation of hepatitis C virus NS5A nonstructural protein: A new paradigm for phosphorylation-dependent viral RNA replication?

Ying Huang, Kirk Staschke, Raffaele De Francesco, Seng-Lai Tan

Virology > 2007 > 364 > 1 > 1-9

The hepatitis C virus (HCV) nonstructural 5A (NS5A) phosphoprotein has been intensely studied due to its ability to subvert the host interferon-induced antiviral response. However, more recent studies suggest that it may also play an important regulatory role in HCV RNA replication as well as modulate host intracellular signaling pathways. Phosphorylation of NS5A appears to be a highly regulated process...

article

Emerging host cell targets for hepatitis C therapy

Yupeng He, Wei Duan, Seng-Lai Tan

Drug Discovery Today > 2007 > 12 > 5-6 > 209-217

Chronic hepatitis C virus (HCV) infection is a major burden on humanity. The current HCV therapy has limited efficacy, and there is pressing need for new and more effective therapies. Host cell factors that are required for HCV infection, replication and/or pathogenesis represent potential therapeutic targets. Of particular interest are cellular receptors that mediate HCV entry, factors that facilitate...

article

The very C-terminus of PRK1/PKN is essential for its activation by RhoA and downstream signaling

Wee Guan Lim, Bee Jen Tan, Yimin Zhu, Shufeng Zhou, more

Cellular Signalling > 2006 > 18 > 9 > 1473-1481

PRK1 is a lipid- and Rho GTPase-activated serine/threonine protein kinase implicated in the regulation of receptor trafficking, cytoskeletal dynamics and tumorigenesis. Although Rho binding has been mapped to the HR1 region in the regulatory domain of PRK1, the mechanism involved in the control of PRK1 activation following Rho binding is poorly understood. We now provide the first evidence that the...

article

The very C-terminus of protein kinase Cɛ is critical for the full catalytic competence but its hydrophobic motif is dispensable for the interaction with 3-phosphoinositide-dependent kinase-1

Yimin Zhu, Derek Smith, Chandra Verma, Wee Guan Lim, more

Cellular Signalling > 2006 > 18 > 6 > 807-818

In this article, we explore the role of the C-terminus (V5 domain) of PKCɛ plays in the catalytic competence of the kinase using serial truncations followed by immune-complex kinase assays. Surprisingly, removal of the last seven amino acid residues at the C-terminus of PKCɛ resulted in a PKCɛ-Δ731 mutant with greatly reduced intrinsic catalytic activity while truncation of eight amino acid residues...

article

Selective role of PKCβ enzymatic function in regulating cell survival mediated by B cell antigen receptor cross-linking

Chandrasekar Venkataraman, Xinyi Cynthia Chen, Songqing Na, Linda Lee, more

Immunology Letters > 2006 > 105 > 1 > 83-89

Cross-linking of the B cell antigen receptor (BCR) results in the activation of several protein tyrosine kinases leading to phospholipase C-γ2-dependent phospholipid hydrolysis and Ca ²⁺ mobilization, followed by activation of the protein kinase C (PKC) family members. Sustained Ca ²⁺ release in B lymphocytes is dependent on the membrane localization and activation of the protein tyrosine...

article

Strategies for hepatitis C therapeutic intervention: now and next

Seng-Lai Tan, Yupeng He, Ying Huang, Michael Gale

Current Opinion in Pharmacology > 2004 > 4 > 5 > 465-470

Interferon-α-based therapies are the mainstay of hepatitis C treatment. However, these broad immunomodulatory agents, already limited by their side effects, expense and route of administration, are not efficacious in all cases. Therefore, research efforts have focused on identifying additional drugs and therapeutic modalities to benefit those individuals refractive to current therapy, and which might...

article

Inactivation of the PKR Protein Kinase and Stimulation of mRNA Translation by the Cellular Co-Chaperone P58 ^IPK Does Not Require J Domain Function ^†

Wei Yan, Michael J. Gale,, Seng-Lai Tan, Michael G. Katze

Biochemistry > 2002 > 41 > 15 > 4938 - 4945

article

How Hepatitis C Virus Counteracts the Interferon Response: The Jury Is Still out on NS5A

Seng-Lai Tan, Michael G. Katze

Virology > 2001 > 284 > 1 > 1-12

Interferons (IFNs) induce an antiviral state in the cell through complex and indirect mechanisms, which culminate in a direct inhibition of viral replication and stimulation of the host adaptive responses. Viruses often counteract with elaborate strategies to interfere with the induction as well as action of IFN effector molecules. This evolutionary battle between viruses and IFN components is a subject...

article

Ser2194 Is a Highly Conserved Major Phosphorylation Site of the Hepatitis C Virus Nonstructural Protein NS5A

Michael G. Katze, Bart Kwieciszewski, David R. Goodlett, Collin M. Blakely, more

Virology > 2000 > 278 > 2 > 501-513

Phosphorylation of the nonstructural NS5A protein is highly conserved among hepatitis C virus (HCV) genotypes. However, the precise site or sites of phosphorylation of NS5A have not been determined, and the functional significance of phosphorylation remains unknown. Here, we showed by two-dimensional phosphopeptide mapping that a protein kinase or kinases present in yeast, insect, and mammalian cells...

article

Using Genetic Means to Dissect Homologous and Heterologous Protein–Protein Interactions of PKR, the Interferon-Induced Protein Kinase

Seng-Lai Tan, Michael G Katze

Methods > 1998 > 15 > 3 > 207-223

The interferon-induced protein kinase, PKR, is a pivotal component of interferon (IFN)-induced cellular antiviral and antiproliferative response. The identification and characterization of proteins, of both viral and cellular origins, that interact with PKR have proven to be a valuable probe for unraveling the cellular regulation and function of PKR. Several studies have demonstrated that PKR forms...

article

Evidence That Hepatitis C Virus Resistance to Interferon Is Mediated through Repression of the PKR Protein Kinase by the Nonstructural 5A Protein

Michael J. Gale, Marcus J. Korth, Norina M. Tang, Seng-Lai Tan, more

Virology > 1997 > 230 > 2 > 217-227

Hepatitis C virus (HCV) is the major cause of non-A non-B hepatitis and a leading cause of liver dysfunction worldwide. While the current therapy for chronic HCV infection is parenteral administration of type 1 interferon (IFN), only a fraction of HCV-infected individuals completely respond to treatment. Previous studies have correlated the IFN sensitivity of strain HCV-1b with mutations within a...

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Search results for: Seng-Lai Tan

Data for the crystal structure of APRIL–BAFF–BAFF heterotrimer

Combined Inhibition of Tumor Necrosis Factor α and Interleukin‐17 As a Therapeutic Opportunity in Rheumatoid Arthritis: Development and Characterization of a Novel Bispecific Antibody

Recent progress and therapeutic perspectives

Bruton's Tyrosine Kinase mediates platelet receptor-induced generation of microparticles: A potential mechanism for amplification of inflammatory responses in rheumatoid arthritis synovial joints

TBK1 Directly Engages Akt/PKB Survival Signaling to Support Oncogenic Transformation

Phosphorylation of hepatitis C virus NS5A nonstructural protein: A new paradigm for phosphorylation-dependent viral RNA replication?

Emerging host cell targets for hepatitis C therapy

The very C-terminus of PRK1/PKN is essential for its activation by RhoA and downstream signaling

The very C-terminus of protein kinase Cɛ is critical for the full catalytic competence but its hydrophobic motif is dispensable for the interaction with 3-phosphoinositide-dependent kinase-1

Selective role of PKCβ enzymatic function in regulating cell survival mediated by B cell antigen receptor cross-linking

Strategies for hepatitis C therapeutic intervention: now and next

Inactivation of the PKR Protein Kinase and Stimulation of mRNA Translation by the Cellular Co-Chaperone P58 ^IPK Does Not Require J Domain Function ^†

How Hepatitis C Virus Counteracts the Interferon Response: The Jury Is Still out on NS5A

Ser2194 Is a Highly Conserved Major Phosphorylation Site of the Hepatitis C Virus Nonstructural Protein NS5A

Using Genetic Means to Dissect Homologous and Heterologous Protein–Protein Interactions of PKR, the Interferon-Induced Protein Kinase

Evidence That Hepatitis C Virus Resistance to Interferon Is Mediated through Repression of the PKR Protein Kinase by the Nonstructural 5A Protein

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