Cytokine receptors are crucial for the maintenance, regulation and growth
of cells in multicellular organisms. As a common theme in cytokine signal-ling, single-span receptor chains are assembled in the cell membrane by a
ligand enabling cross-activation of the aligned cytoplasmic receptor
Mycobacteria are endowed with mechanisms through which they can evade the onslaught ofhost defense response. These mechanisms are discussed including diminishing the ability ofantigen presenting cells to present antigens to CD4+ T cells; production of suppressive cytokines;escape from fused phagosomes and inducing T cell apoptosis.
Erythropoietin (Epo) is a hematopoietic cytokine that is
crucial for the differentiation and proliferation of erythroid
progenitor cells. Epo acts on its target cells by inducing
homodimerization of the erythropoietin receptor (EpoR),
thereby triggering intracellular signaling cascades. The
EpoR encompasses eight tyrosine motifs on its cytoplasmic
tail that have been shown to recruit a number of regulatory
The protein arginine methyltransferase (PRMT) family of enzymes cata-lyzes the transfer of methyl groups from S-adenosylmethionine to the gua-nidino nitrogen atom of peptidylarginine to form monomethylarginine or
dimethylarginine. We created several less polar analogs of the specific
PRMT inhibitor arginine methylation inhibitor-1, and one such compound
was found to have improved PRMT inhibitory activity over the parent
Staphylococcus aureusand Streptococcus pyogenes(group A streptococci)
are Gram-positive pathogens capable of producing a variety of bacterial exo-toxins known as superantigens. Superantigens interact with antigen-present-ing cells (APCs) and T cells to induce T cell proliferation and massive
cytokine production, which leads to fever, rash, capillary leak and subse-quent hypotension, the major symptoms of toxic shock syndrome.
Developing thymocytes and T cells express the Tec kinases Itk, Rlk⁄Txk
and Tec, which are critical modulators of T-cell receptor signaling, required
for full activation of phospholipase Cc, and downstream Ca
and ERK-mediated signaling pathways.
Stress-activated protein kinase (SAPK) signaling plays essential roles in eliciting adequate cellular responses to stresses and proinﬂammatory cytokines. SAPK pathways are composed of three successive protein kinase reactions. The phosphorylation of SAPK signaling components on Ser/Thr or Thr/Tyr residues suggests the involvement of various protein phosphatases in the negative regulation of these systems.
Cancer, although a dreadful disease, is at the same time a fascinating biological
phenotype. Around 1980, cancer was first attributed to malfunctioning genes and,
subsequently, cancer research has become a major area of scientific research supporting
the foundations of modern biology to a great extent. To unravel the human
genome sequence was one of those extraordinary tasks, which has largely
been fuelled by cancer research, and many of the fascinating insights into the
genetic circuits that regulate developmental processes have also emerged from
research on cancer....
The cystine-knot motif, made up of three intertwined disulfide bridges, is a
unique feature of several toxins, cyclotides and growth factors, and occurs
in a variety of species, including fungi, insects, molluscs and mammals.
Growth factor molecules containing the cystine-knot motif serve as ligands
for a diverse range of receptors and play an important role in extracellular
Tumour necrosis factor-a(TNF-a) is a cytokine that is involved in many
functions, including the inflammatory response, immunity and apoptosis.
Some of the responses of TNF-a are mediated by caspase-1, which is
involved in the production of the pro-inflammatory cytokines interleukin-1b, interleukin-18 and interleukin-33.
Peripheral nerve injury is normally followed by a robust regenerative
response. Here we describe the early changes associated with injury from
the initial rise in intracellular calcium and the subsequent activation of
transcription factors and cytokines leading to an inflammatory reaction,
and the expression of growth factors, cytokines, neuropeptides, and other
secreted molecules involved in cell-to-cell communication promoting regen-eration and neurite outgrowth.
The ultimate goal of cancer research is the development of effective anticancer
therapy. During the last several decades, the discovery of oncogenes, tumor
suppressors, growth factors, signal transduction pathways has dramatically
escalated our understanding of cancer cell biology and mechanisms of cell
transformation.1-3 Hundreds of cellular proteins and pathways have been logically
considered as molecular targets in a mechanism-based approaches of anticancer drug
Yet, the progress in cancer treatment has not paralleled these dramatic achievements
in basic research.
Therapeutic immunosuppression has very broad applications in clinical medicine,
ranging from prevention and treatment of organ and bone marrow transplant
rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis),
skin diseases, allergies and asthma. Whereas traditionally only a small repertoire of
immunosuppressive agents was available for clinical use, recent discoveries have
significantly increased the number of approved agents, resulting in numerous trials to
further evaluate their potential.
The molecular definition of tumor antigens, costimulatory signals, and the
possibility to genetically engineer tumor cells as well as simple protocols for
efficient isolation and preparation of dendritic cells (DC) renew the interest in
tumor immunotherapy and vaccination, in particular. Engineering of tumor
cells with the gene of a particular cytokine is a way of releasing that cytokine at
the tumor site. In contrast to bolus administration, it provides a constant supply
This book has been made possible by the contributions of leading scientists and clinicians from upcoming and interdisciplinary fields of research concerning the molecular and clinical features of insulin resistance. Multiple metabolic disturbances associated with Insulin Resistance include inflammatory cytokines, adipokines, endothelial dysfunction, tissue-specific defects in insulin action and signaling, oxidative stress, ectopic lipid deposition, and disordered neuroregulation.
Interleukin (IL)-6-type cytokines exert their effects through activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade. The JAK/STAT pathways play an important role in rheumatoid arthritis, since JAK inhibitors have exhibited dramatic effects on rheumatoid arthritis (RA) in clinical trials. In this study, we investigated the molecular effects of a small molecule JAK inhibitor, CP690,550 on the JAK/STAT signaling pathways and examined the role of JAK kinases in rheumatoid synovitis....
Subunits (a, b and c) of the interleukin-2 receptor complex (IL-2R) are involved in both proliferative and activationinduced cell death (AICD) signaling of T cells. In addition, the signaling b and c chains are shared by other cytokines (e.g. IL-7, IL-9, IL-15). However, the molecular mechanisms responsible for recruiting/sorting the a chains to the signaling chains at the cell surface are not clear.
The proliferation of smooth muscle cells (SMC) is a key
event in the development of atherosclerosis. In addition to
growth factors or cytokines, we have shown previously that
n-3 polyunsaturated fatty acids (PUFAs) act in opposition
to n-6 PUFAs by modulating various steps of the inflam-matory process. We have investigated the molecular mech-anisms by which the incorporation of the n-6 PUFA,
arachidonic acid, increases the proliferation of rat SMC
treated with interleukin-1b, while the n-3 PUFAs eicosa-pentaenoic acid (EPA) and docosahexaenoic acid (DHA),
elicit nomitogenic response. ...