Disease relevance of Signal Transduction

• Abnormalities in the signal-transduction pathways for granulocyte colony-stimulating factor (G-CSF) may play a part in the progression to acute myeloid leukemia [1].
• A single-point mutation in the TIR domain of murine TLR4 (Pro712His, the Lps(d) mutation) abolishes the host immune response to lipopolysaccharide (LPS), and mutation of the equivalent residue in TLR2, Pro681His, disrupts signal transduction in response to stimulation by yeast and gram-positive bacteria [2].
• These findings indicate that antagonists of PRL/PRL receptor interaction or PRL receptor-associated signal transduction may be of considerable utility in the treatment of human breast cancer [3].
• The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression [4].
• These results show that the signals initiated by CD2 and CD3 can be regulated independently within the same T cell; uncoupling of signal transduction after antigen-specific stimulation provides a biochemical mechanism to explain, in part, the profound immunodeficiency of patients with HIV-1 infection [5].

Psychiatry related information on Signal Transduction

• Attenuation of the phosphatidylinositol (PI) signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as the mechanism for the efficacy of Li+ in the treatment of bipolar disorder [6].
• These observations suggest that BTH treatment can compensate only partially for an impaired signal transduction pathway and support the idea that pathogen defense mechanisms are under positive feedback control [7].
• We hypothesize that impaired synaptic plasticity and associated memory dysfunction during early stage Alzheimer's disease and severe cellular degeneration and dementia during end stage could be caused by the biphasic impact of Abeta-derived diffusible ligands acting upon particular neural signal transduction pathways [8].
• Several signal transduction pathways have been implicated in classical conditioning of this preparation, although the major emphasis has been on protein kinase C. Here we provide evidence for the activation and phosphorylation of a mitogen-activated protein kinase (MAPK) pathway by one-trial and multi-trial conditioning [9].
• To the extent that the defects in signal transduction and in active electrical properties, including synaptic plasticity, that are found in the Ts16 and Ts65Dn mouse models, are found in the brain of DS subjects, we postulate that mental retardation in DS results from such abnormalities [10].

High impact information on Signal Transduction

• A shared feature of signal transduction downstream of most receptors on immune cells, as in nonhematopoietic cell types, is the activation of phosphoinositide 3-kinase (PI3K) [11].
• Chemokine messages are decoded by specific receptors that initiate signal transduction events leading to a multitude of cellular responses, leukocyte chemotaxis and adhesion in particular [12].
• The FcalphaRI alpha chain lacks canonical signal transduction domains but can associate with the FcR gamma-chain that bears an activation motif (ITAM) in the cytoplasmic domain, allowing activatory functions [13].
• The CIS family of proteins (also referred to as the SOCS or SSI family) has been implicated in the regulation of signal transduction by a variety of cytokines [14].
• Studies of signal transduction have begun to determine the basis for the coreceptor activities of CD19 [15].

Chemical compound and disease context of Signal Transduction

• These results indicate that the guanylate cyclase-coupled ANF receptor exists in a 180-kilodalton protein of rat adrenocortical carcinoma and represent a step toward the elucidation of the basic mechanism of cyclic GMP-mediated transmembrane signal transduction in response to a hormone [16].
• Inhibition of T cell receptor signal transduction by tyrosine kinase-interacting protein of Herpesvirus saimiri [17].
• Differences in Ca++ mobilization and sensitivity to pertussis toxin suggest that tryptase and thrombin activate distinct signal transduction pathways in fibroblasts [18].
• Insulin resistance, which may precede the development of non-insulin-dependent diabetes mellitus in Pima Indians, appears to result from a postreceptor defect in signal transduction in skeletal muscle [19].
• Recent successes using Gleevec for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors have provided proof that strategies to target signal transduction pathways mutated in human cancers can work [20].

Biological context of Signal Transduction

• Widespread localization, responsiveness to numerous signal transduction systems, and broad substrate specificity enable the multifunctional CaM kinase to mediate regulation of many cellular functions [21].
• Our results demonstrate that loss of Dnmt1 causes cell-type-specific changes in gene expression that impinge on several pathways, including expression of imprinted genes, cell-cycle control, growth factor/receptor signal transduction and mobilization of retroelements [22].
• FAR1 links the signal transduction pathway to the cell cycle machinery in yeast [23].
• Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and impaired responsiveness to GTPase activating proteins, render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage-specific manner [24].
• Down-regulation of the Drosophila morphogen bicoid by the torso receptor-mediated signal transduction cascade [25].

Anatomical context of Signal Transduction

• The external domain of CD45 does not appear to be absolutely required for signal transduction by the T cell receptor, and there is currently no evidence that ligand binding modulates CD45 activity [26].
• CD45 is now established as a critical component of the signal transduction machinery of lymphocytes [26].
• Binding of alpha factor to Ste2p, a G protein-coupled plasma membrane receptor, activates a signal transduction pathway and stimulates endocytosis of the receptor-ligand complex [27].
• These studies identify a rapamycin-sensitive signaling pathway, argue for a ubiquitous role for FKBPs in signal transduction, indicate that FK506-FKBP-calcineurin complexes do not interfere with pp70S6K signaling, and show that in fibroblasts pp70S6K, not RSK, is the physiological S6 kinase [28].
• TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells [29].

Associations of Signal Transduction with chemical compounds

• The mechanisms by which these inhibitors of cytokine signal transduction exert their effects have been extensively studied and will provide useful information for regulating tyrosine-kinase activity [14].
• Multiple mechanisms of androgen independence have now been documented, including amplification of the androgen receptor as well as signal transduction pathways that bypass the androgen receptor completely [30].
• Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase and a response regulator protein [31].
• Highly enriched in brain tissue and present throughout the body, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is central to the coordination and execution of Ca(2+) signal transduction [32].
• As a serine/threonine protein phosphatase, calcineurin participates in a number of cellular processes and Ca(2+)-dependent signal transduction pathways [33].

Gene context of Signal Transduction

• The third component, the gamma chain, of IL-2 receptor plays a pivotal role in formation of the full-fledged IL-2 receptor, together with the beta chain, the gamma chain participates in increasing the IL-2 binding affinity and intracellular signal transduction [34].
• Notably, platelet-derived growth factor receptor alpha (PDGFRA) and members of the downstream RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors [35].
• IFN-alpha/beta receptor is physically associated with the cytoplasmic Tyr kinase JAK1, hence, in addition to ligand binding, it is directly involved in signal transduction [36].
• These results suggest that N-SMase and A-SMase control important yet dissociable and nonoverlapping pathways of TNF receptor signal transduction [37].
• This is the first in vivo demonstration of leptin signal transduction [38].

Analytical, diagnostic and therapeutic context of Signal Transduction

• The initiation of biochemical signal transduction following ligation of surface receptors with intrinsic cytoplasmic tyrosine kinase activity is common for many cell types [39].
• To generate animal models for human diseases involving the gonadotropin signal transduction pathway, we produced mice deficient in the FSH beta subunit and therefore in FSH using ES cell technology [40].
• Suppressor of cytokine signalling-2 (SOCS-2) is a member of the suppressor of cytokine signalling family, a group of related proteins implicated in the negative regulation of cytokine action through inhibition of the Janus kinase (JAK) signal transducers and activators of transcription (STAT) signal-transduction pathway [41].
• We report the molecular cloning and sequence of a phosphoinositide-specific phospholipase C (PI-PLC), an enzyme that is of particular interest because of its central role in cell signal transduction [42].
• These engineered receptors can function as biosensors for their new ligands; we also incorporated them into synthetic bacterial signal transduction pathways, regulating gene expression in response to extracellular trinitrotoluene or l-lactate [43].

References