Biomedical subjects

S Pellegrini

Publications and source records attributed to S Pellegrini.

At least 19 recordsLinked to original sources

PubMed2006

Carpal tunnel syndrome and ulnar neuropathy at the elbow in floor cleaners.

OBJECTIVE: To determine the occurrence of carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in a cohort of floor cleaners and to check differences between workers with and without CTS. METHODS: All female floor cleaners of three major hospitals in Tuscany (Italy) were contacted. Clinical and electrophysiological severity of CTS and UNE were evaluated with standardized scales and symptoms were assessed with the self-administered Boston Questionnaire (BQ); demographic and non-occupational factors and durations of current and previous occupations were recorded. Univariate analysis of risk factors was performed in workers with and without CTS. Logistic regression was used to evaluate the capacity of independent variables to predict CTS. RESULTS: Out of a total of 179 cleaners, 145 (81%)-mean age 39.6 years (20-64 years)-were enrolled in the study; 70 (48%) had CTS (diagnosis based on clinical and electrophysiological findings). BQ symptom and hand function scores were anomalous in 108 (74%) and 84 (58%) subjects, respectively. UNE was detected in 7/103 women. Univariate analysis showed that cleaners with CTS were older, had greater BMI and longer exposure to cleaning with previous employers than those without CTS. In the logistic regression, the only predictor of CTS was cleaning with previous employers (O.R. 12.1, 95% CI 3-49.9). CONCLUSIONS: These results indicate a high occurrence of CTS in floor cleaners; UNE is less frequent than CTS, presumably due to repetitive movements that stress wrists more than elbows. The only predictive factor of CTS was cleaning as an occupation with previous employers. Therefore, the actual risk factor for CTS could not be cleaning per se, but how this job is performed.

Adult↗

PubMed2006

[Human cost of low back pain: a multi-disciplinary approach].

The valuation of human costs is a necessity, but this task poses many problems of method. A team made of a philosopher, a psychologist and a physician has been working with economist researchers in order to look into the meaning that the preferences announced at the time of the inquiries on human costs by QALY methods could assume. These methods are often used to obtain a valuation of the impact of a health attack on people's quality of life. The methods--in the frame of the argument assumed by the economic theory on well-being--hypothesize that people's choices depend mainly on cognitive work. The qualitative interviews show that the psychological construction process for the announced preferences largely overlap this frame. In this paper the authors hastily tackle the factors which have an effect on the preferences. They conclude that the QALY methods don't seem to be able to assess the quality of life nori to valuate the damage that the quality of life could include.

Cost of Illness↗

PubMed2006

Negative regulation of type I interferon signaling: facts and mechanisms.

Initially described for their antiviral activities, type I Interferons are now recognized as central regulatory elements of the immune response, primarily for their effect on the differentiation of monocytes into dendritic cells and osteoclasts. They are routinely used in clinic for the treatment of several diseases, including viral hepatitis, multiple sclerosis and several forms of cancer. Interferons are however not devoid of toxic effects when high doses are administered to patients, indicating that interferon action must be timely and spatially down regulated. We review here the molecular mechanisms which have been described to shut off the interferon initiated signals.

Animals↗

PubMed2006

Chronic urticaria: importance of a medical-psychological approach.

Chronic urticaria is often associated with psychological factors, such as depression, anxiety and stress, which may play a role not only in the genesis of the disease but also in its evolution. Aims of this study were to evaluate the utility of psychological assessments (presence of depression, impact on the quality of life and incidence of "life events" before the beginning of urticaria) in conjunction with the allergological evaluation and to provide appropriate treatment to the patients selected. Thirty subjects diagnosed as Chronic Urticaria patients were submitted to psychological assessments (semi structured interview, Beck Depression Inventory, Nottingham health Profile and Dermatology Life Quality Index). The results of the evaluation show that most of the patients experienced a "stressor" event within the six months before the onset of the cutaneous manifestation. The incidence of depression resulted very high in comparison with the general population and in three cases at a severe level. The impact on the quality of life results to be moderate, but involving different fields of life (physical image, social life, quality of sleeping and eating, etc). Despite these results, only six patients accepted to be assigned to an appropriate treatment. In conclusion, we demonstrate the usefulness of a medical- psychological approach in chronic urticaria and we confirmed the resistance of psychosomatic patients to undergo psychological treatment.

Activities of Daily Living↗

PubMed2004

Embryonic soluble HLA-G as a marker of developmental potential in embryos.

BACKGROUND: In human reproduction, embryo implantation is complex and poorly understood. At present, no single markers are used in routine treatment to assay biochemical functions of the human embryo. Soluble human leukocyte antigen-G (sHLA-G) could be considered a possible marker of embryo developmental potential. It is localized primarily on the extravillous trophoblast, making this antigen a potential mediator of immune interaction at the maternal-fetal interface during gestation. METHODS: Soluble-HLA-G levels were evaluated by an enzyme-linked immunosorbent assay (ELISA) employing monoclonal antibody MEM-G9. It was evaluated in 318 media of single embryo cultures. We correlated the presence of sHLA-G with embryo morphology and the pregnancy obtained in that treatment cycle. RESULTS: No correlation was found between embryo morphology and sHLA-G levels. Pregnancy was observed only when the medium of at least one transferred embryo contained sHLA-G. In 26 out of 66 patients, none of the obtained embryos showed any detectable sHLA-G molecules and no pregnancy occurred. CONCLUSIONS: From our results, we propose sHLA-G as a potential marker of embryo development: the sHLA-G ELISA can be a useful biochemical assay in addition to embryo morphology in embryo selection for transfer in IVF treatment if there are other embryos with the same morphology.

Biomarkers↗

PubMed2003

Causative and susceptibility genes for Alzheimer's disease: a review.

Alzheimer's disease (AD) is the most common type of dementia in the elderly population. Three genes have been identified as responsible for the rare early-onset familial form of the disease: the amyloid precursor protein (APP) gene, the presenilin 1 (PSEN1) gene and the presenilin 2 (PSEN2) gene. Mutations in these genes, however, account for less than 5% of the total number of AD cases. The remaining 95% of AD patients are mostly sporadic late-onset cases, with a complex aetiology due to interactions between environmental conditions and genetic features of the individual. In this paper, we review the most important genes supposed to be involved in the pathogenesis of AD, known as susceptibility genes, in an attempt to provide a comprehensive picture of what is known about the genetic mechanisms underlying the onset and progression of AD. Hypotheses about the role of each gene in the pathogenic pathway are discussed, taking into account the functions and molecular features, if known, of the coded protein. A major susceptibility gene, the apolipoprotein E (APOE) gene, found to be associated with sporadic late-onset AD cases and the only one, whose role in AD has been confirmed in numerous studies, will be included in a specific chapter. As the results reported by association studies are conflicting, we conclude that a better understanding of the complex aetiology that underlies AD may be achieved likely through a multidisciplinary approach that combines clinical and neurophysiological characterization of AD subtypes and in vivo functional brain imaging studies with molecular investigations of genetic components.

Alzheimer Disease↗

PubMed2003

Endothelium and the brain in CNS lupus.

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is common and results in different clinical manifestations. Several pathogenic mechanisms have been suggested to play a role in determining such a variety of clinical symptoms. The thrombophilic state associated to the presence of antiphospholipid antibodies has been suggested to be responsible for a noninflammatory vasculopathy which causes clear ischaemic events as well as alterations of the cerebral microcirculation that are likely associated to seizures, cognitive dysfunction or psychosis. Although less frequent, a true vasculitic process affecting cerebral circulation has also been reported. In both cases, brain endothelium does represent the target of the pathogenic mechanisms. Brain endothelial cells display peculiar functional and phenotypical characteristics in comparison with endothelial cells from other anatomical districts, raising the possibility that this might be the reason for its susceptibility in lupus disease. We review and present data suggesting that a higher and firmer expression of beta 2 glycoprotein I on endothelial cell membranes can be responsible for a selective damage/activation by circulating anti-beta 2 glycoprotein I, and that antiendothelial cell antibodies crossreact with brain endothelium and in some cases, specifically bind brain endothelial cells only in lupus patients with central nervous involvement.

Animals↗

PubMed2003

Effect of resveratrol and catechin on PC12 tyrosine kinase activities and their synergistic protection from beta-amyloid toxicity.

beta-Amyloid peptide (beta-AP) is the main component of amyloid deposits around the cerebral vessel and in the brain parenchyma in Alzheimer's disease and Down's syndrome. In vitro studies in neuronal cells or in PC12 and Hela cell lines have shown that the aggregate form of beta-AP is toxic. Many genetic and environmental factors including metal ions, proteoglycans, plasma proteins and antioxidants modify beta-AP toxicity. We investigated the effect of two plant polyphenols--resveratrol and catechin--on soluble and particulate tyrosine kinase activity from PC12 cells and the protective action of these compounds against beta-AP (1-41) toxicity. beta-AP (1-41) decreased PC12 viability with an IC50 value of 1.1 +/- 0.14 x 10(-8) M. Resveratrol and catechin protected PC12 cells from beta-AP (1-41) toxicity. With 25 microM resveratrol the IC50 value increased to 2.2 +/- 0.19 x 10(-7) M. In the presence of beta-AP (1-41) resveratrol showed a concentration-dependent biphasic effect, and at a concentration of up to 40 microM it protected PC12 cells from beta-AP (1-41) toxicity. At concentrations higher than 40 microM, an inhibitory activity on cell proliferation appeared. This antiproliferative effect was also seen in the absence of beta-AP (1-41). With 100 microM catechin the IC50 value increased from 1.1 +/- 0.14 x 10(-8) M to 3.2 +/- 0.25 x 10(-7) M beta-AP (1-41). The protective effect was concentration dependent. Resveratrol and catechin had a synergistic protective action. In the presence of 40 microM catechin and 10 microM resveratrol or 20 microM resveratrol and 10 microM catechin, the toxicity determined by 10(-7) M beta-AP (1-41) was almost completely removed. Resveratrol and catechin had different effects on PC12 tyrosine kinase activity. With peptide 1-17 of gastrin as substrate, resveratrol inhibited particulate tyrosine kinases while it had no effect on soluble activity. With the same substrate, catechin increased the activity of soluble fraction while it inhibited particulate activity. When peptide 6-20 of cell division kinase p34cdc2 was utilized, catechin showed an opposite effect, inhibiting soluble tyrosine kinase activity and increasing particulate activity. With peptide 6-20, resveratrol inhibited both soluble and particulate activities. These results demonstrate that resveratrol and catechin have different activities on the signal transduction pathway involving protein phosphorylation. These differences may contribute not only to the different effects of these compounds on PC12 growth but also to the synergistic effect against beta-AP (1-41) toxicity. The different activity of resveratrol and catechin on signal transduction pathways, as well as the differences in metal chelation, partition coefficient between water and lipids, hydrogen donation redox potential and enzyme inhibition may be at least in part based on synergistic protection against beta-AP (1-41) toxicity.

Amyloid beta-Peptides↗

PubMed2001

Down-modulation of type 1 interferon responses by receptor cross-competition for a shared Jak kinase.

In contrast to the large number of class I and II cytokine receptors, only four Janus kinase (Jak) proteins are expressed in mammalian cells, implying the shared use of these kinases by many different receptor complexes. Consequently, if receptor numbers exceed the amount of available Jak, cross-interference patterns can be expected. We have engineered two model cellular systems expressing two different exogenous Tyk2-interacting receptors. A receptor chimera was generated wherein the extracellular part of the interferon type 1 receptor (Ifnar1) component of the interferon-alpha/beta receptor is replaced by the equivalent domain of the erythropoietin receptor. Despite Tyk2 activation, erythropoietin treatment of cells expressing this erythropoietin receptor/Ifnar1 chimera did not evoke any detectable IFN-type response. However, a dose-dependent interference with signal transduction via the endogenous Ifnar complex was found for STAT1, STAT2, STAT3, Tyk2, and Jak1 activation, for gene induction, and for antiviral activity. In a similar approach, cells expressing the beta1 chain of the interleukin-12 receptor showed a reduced transcriptional response to IFN-alpha as well as reduced STAT and kinase activation. In both model systems, titration of the Tyk2 kinase away from the Ifnar1 receptor chain accounts for the observed cross-interference.

Animals↗

PubMed2001

The receptor interaction region of Tyk2 contains a motif required for its nuclear localization.

Janus kinases have so far been viewed as enzymatic intermediates that couple a variety of cell surface receptors to downstream substrates with diverse effector functions. Tyk2 is a member of this family that is involved in the interferon-alpha/beta and interleukin-12 signaling pathways via its specific interaction with the IFNAR1 and the beta1 receptor subunits. Here, we have analyzed the subcellular distribution of the wild-type Tyk2 protein and of several mutants expressed in Tyk2-deficient human cells. Direct GFP-associated fluorescence and immunostaining showed a diffuse localization of Tyk2 throughout the cell, including the nuclear compartment. The nuclear localization of Tyk2 requires a nuclear localization signal-like motif rich in arginine residues that maps within the region mediating interaction with cytokine receptors. To address the question of the role of the Tyk2 nuclear pool in interferon-alpha/beta-induced biological effects, cells expressing a membrane-targeted form of Tyk2-green fluorescent protein were analyzed for their interferon-alpha responses. Our studies demonstrate that Tyk2 can reside in the nucleus independently of receptor binding and that the nuclear pool is dispensable for the transcriptional and anti-vesicular stomatitis virus responses induced by interferon-alpha.

Amino Acid Motifs↗

PubMed2001

Production of IL-4 and leukemia inhibitory factor by T cells of the cumulus oophorus: a favorable microenvironment for pre-implantation embryo development.

The nature and the functional activity of immunocytes present in the cumulus oophorus, a mass of cells surrounding the oocyte, were examined here for the first time. The cumuli oophorus were obtained from women who had taken part in an in vitro fertilization program and were suffering from blocked fallopian tubes. Both macrophages and CD4(+) T cells were detected in all cumuli. CD4(+) T cell clones, generated from T cells of these cumuli, showed higher potential to produce IL-4 and leukemia inhibitory factor (LIF) than CD4(+) T cell clones generated from peripheral blood or ovary specimens from the same women. More importantly, IL-4 and LIF, but not IFN-gamma mRNA was found to be constitutively expressed in vivo by cumulus oophorus cells. Progesterone is highly produced by the cumulus oophorus/oocyte complex. We recently showed that progesterone up-regulates the production of LIF by T cells and that the progesterone-induced LIF production is mediated by IL-4. Progesterone produced by cumulus granulosa cells may favor IL-4 production by T cells, which in turn can produce LIF. As the treatment with LIF enhances the in vitro growth and development of mammalian embryos, our data suggest that T cells present in the cumulus oophorus produce cytokines that may provide a microenvironment suitable for pre-implantation development of the mammalian embryo.

Adult↗

PubMed2001

Reduced expression of INT-6/eIF3-p48 in human tumors.

The int-6 gene, originally identified as a common integration site for the mouse mammary tumor virus (MMTV) in mouse mammary tumors, encodes the p48 component of the eukaryotic translation initiation factor-3 (eIF3-p48). Int-6/eIF3-p48 is expressed in all adult tissues which have been tested and early in embryonic development. Int-6/eIF3-p48 has been highly conserved throughout evolution and the deduced amino acid sequence of the human gene product is identical to the mouse protein. Viral insertions at the Int-6/eIF3-p48 locus in mouse mammary tumors result in production of chimeric Int-6/eIF3-p48/MMTV products that may act as dominant negative oncoproteins. Int-6/eIF3-p48 has also been identified as a human protein that binds to the human T-cell leukemia virus type I Tax oncoprotein. The role of Int-6/eIF3-p48 in human carcinogenesis is unknown at the present time. In this study we have examined Int-6/eIF3-p48 gene status and expression in two of the most common forms of cancer in humans, breast and lung tumors. Sixty-two breast carcinomas and 78 non-small cell lung carcinomas (NSCLC) were investigated. LOH at the Int-6/eIF3-p48 locus was observed in 5 (21%) of 24 informative breast tumors and 10 (29%) of 34 informative lung tumors. A reduced expression of Int-6/eIF3-p48 was seen in 23 (37%) of breast cancer samples and 24 (31%) of NSCLC samples. An association between Int-6/eIF3-p48 expression and LOH at the Int-6/eIF3-p48 locus was observed. Int-6/eIF3-p48 expression was not related to commonly used pathological parameters in breast cancer patients, while in NSCLC patients int-6/eIF3-p48 expression was mainly seen in adenocarcinomas (P<0.0001). In conclusion, our data show for the first time a decreased expression of Int-6/eIF3-p48 in a consistent portion of human breast and lung carcinomas, frequently associated with LOH at the Int-6/eIF3-p48 locus. Additional studies on larger series of tumor specimens with long-term follow-up are needed to determine whether Int-6/eIF3-p48 expression may represent a new prognostic or predictive marker.

Biomarkers, Tumor↗

PubMed2000

A dual role for the kinase-like domain of the tyrosine kinase Tyk2 in interferon-alpha signaling.

Tyrosine kinases of the Janus kinase family initiate cellular responses through their association with receptors for alpha-helical cytokines. In addition to a tyrosine kinase domain, these enzymes possess a kinase-like (KL) domain, whose function remains elusive. To investigate the role of the KL domain of Tyk2 in interferon-alpha/beta signaling, we transfected a library of Tyk2 cDNAs containing random point mutations in KL into Tyk2-negative cells and selected for loss-of-function Tyk2 mutants. Four such mutants, V584D, G596V, H669P, and R856G, were identified through this screen. Like the wild-type Tyk2, the mutant proteins were able to sustain the level of IFNAR1 receptor protein. However, all four mutants were incapable of restoring high-affinity interferon-alpha binding in Tyk2-negative cells and were also catalytically impaired, even when transiently overexpressed. Interferon-alpha induced phosphorylation, and gene expression could be detected in V584D- or G596V-expressing cells, but not in H669P- or R856G-expressing cells. Furthermore, H669P and R856G proteins were constitutively highly phosphorylated. All together, our findings demonstrate that an intact KL domain is essential for the intrinsic catalytic activity of Tyk2 and for the establishment of a high-affinity interferon-alpha receptor complex.

Cell Line↗

PubMed2000

A morphological study of the expression of the small G protein RhoA in resting and activated MDCK cells.

The small G protein Rho subfamily controls several cellular events such as growth, movement, proliferation and differentiation by rearranging actin and cytoskeleton proteins. Most of these effects are mediated by the activation of growth factor and extracellular matrix molecule receptors, suggesting a role for Rho molecules in the transduction pathway of these receptors. Despite the importance of Rho peptides in fundamental cellular events, data on their subcellular immunolocalisation are sparse: here we investigated the expression and subcellular localisation of RhoA in resting (cultured on plastic) and activated (Matri-cell or hepatocyte growth factor) MDCK cells by immunoperoxidase and immunogold techniques. Resting MDCK cells contain detectable amounts of RhoA mainly localised in the cytoplasm; RhoA expression is significantly enhanced by Matri-cell substrates that promote translocation of RhoA at the membrane level. This enhancing effect is reduced after exposure to hepatocyte growth factor.

Animals↗

PubMed2000

The distribution of neuropeptide Y-immunoreactive neurons and nerve fibers in the forebrain of the carp Cyprinus carpio L.

The present study reports the distribution of Neuropeptide Y (NPY)-immunoreactive neurons and fibers in the forebrain of the adult carp Cyprinus carpio L. Serial Nissl-stained sections were used for cytoarchitecture and identification of anatomical structures. Immunostaining of NPY-containing neurons and fibers was used as neurochemical marker and tool for comparison with other species, including the goldfish. The general outline of the cytoarchitecture of the carp forebrain is similar to that of other Cypriniformes. However, using NPY immunohistochemistry, we found several specific differences with the goldfish, especially in the diencephalon. In the hypothalamus of the carp NPY-immunoreactive (NPYir) neurons were identified in the n. dorsolateralis thalami, and in the n. ventralis lateralis thalami. In the same location, we observed the n. anterior hypothalami and the n. preglomerulosus pars lateralis, described in the goldfish, as parts of n. prerotundus. However, in the carp we were not able to identify a n. preglomerulosus pars medialis, a n. preglomerulosus pars medialis commissuralis and a n. glomerulosus. We describe a n. rotundus, in which we did not find substructures typical of the goldfish. Further differences with the goldfish, trout and salmon were also noted.

Animals↗

PubMed1999

The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha.

We have examined the effects of human papilloma virus (HPV) E6 proteins on interferon (IFN) signaling. Here we show that expression of the 'malignant' HPV-18 E6 in human HT1080 cells results in inhibition of Jak-STAT activation in response to IFN-alpha but not IFN-gamma. This inhibitory effect is not shared by the 'benign' HPV-11 E6. The DNA-binding and transactivation capacities of the transcription factor ISGF3 are diminished in cells expressing HPV-18 E6 after IFN-alpha treatment as a result of decreased tyrosine phosphorylation of Tyk2, STAT2 and STAT1. However, HPV-18 E6 does not affect the induction of tyrosine phosphorylation and DNA-binding of STAT1 by IFN-gamma. In addition, HPV E6 proteins physically interact with Tyk2. This interaction takes place preferably with HPV-18 E6 and to a lesser extent with HPV-11 E6. The E6/Tyk2 interaction requires the JH6-JH7 domains of Tyk2, which are important for Tyk2 binding to the cytoplasmic portion of IFN-alpha receptor 1 (IFNAR1). These findings demonstrate an inhibitory role of HPV-18 E6 in the IFN-alpha-induced Jak-STAT pathway, which may be explained, at least in part, by the ability of E6 to interact with and impair Tyk2 activation.

Cell Line↗

PubMed1999

Downregulation of interleukin-12 (IL-12) responsiveness in human T cells by transforming growth factor-beta: relationship with IL-12 signaling.

Interleukin-12 (IL-12) is a cytokine that plays a central role in the control of cell-mediated immunity. We have previously shown that transforming growth factor-beta1 (TGF-beta) inhibitory effects on human primary allogeneic cytotoxicity and proliferative responses interfere with IL-12 pathway. The present study was undertaken to further elucidate the biochemical basis of the functional interaction between these two cytokines and to define the site of TGF-beta action on the signaling pathway activated by IL-12. Our data indicate that TGF-beta induced an inhibition of interferon-gamma (IFN-gamma) production without affecting the IL-12Rbeta1 and IL-12Rbeta2 subunits mRNA expression by activated T cells. We further show that TGF-beta has a significant inhibitory effect on the early signal transduction events following interaction of IL-12 with its receptor on activated T cells, resulting in the inhibition of both JAK2 and Tyk2 phosphorylation. In addition, TGF-beta was found to significantly inhibit IL-12-induced phosphorylation of the STAT4 transcription factor. Electrophoretic mobility shift assay indicated that TGF-beta induced a decrease in IL-12-induced STAT4 DNA binding activity in T lymphocytes. This study suggests that TGF-beta influences IL-12 responsiveness at least in part by inhibiting early signaling events essential to gene induction in IL-12-activated T cells.

Cells, Cultured↗

PubMed1999

Induction of beta-R1/I-TAC by interferon-beta requires catalytically active TYK2.

The beta-R1/I-TAC (interferon-inducible T-cell alpha-chemoattractant) gene encodes an alpha-chemokine that is a potent chemoattractant for activated T-cells. We previously reported that beta-R1 was selectively induced by interferon (IFN)-beta compared with IFN-alpha and that the canonical type I IFN transcription factor interferon-stimulated gene factor 3 (ISGF3) was necessary but not sufficient for beta-R1 induction by IFN-beta. These findings suggested that beta-R1 induction by IFN-beta required an accessory component. To begin characterizing this signaling pathway, we examined the function of TYK2 protein in the IFN-beta-mediated induction of beta-R1. This study was motivated by the observation that beta-R1 could not be induced in TYK2-deficient U1 cells by IFN-beta (Rani, M. R. S., Foster, G. R., Leung, S., Leaman, D., Stark, G. R., and Ransohoff, R. M. (1996) J. Biol. Chem. 271, 22878-22884), an unexpected result because IFN-beta evokes substantial expression of IFN-stimulated genes (ISGs) in U1 cells through a TYK2-independent pathway. We now report beta-R1 expression patterns in U1 cells complemented with wild-type or mutant TYK2 proteins. Complementation with wild-type TYK2 rescued IFN-beta-inducible expression of beta-R1. Cells expressing kinase-deficient deletion or point mutants of TYK2 were refractory to induction of beta-R1 by IFN-beta despite robust expression of other ISGs. Transient transfection analysis of a beta-R1 promoter-reporter confirmed that transcriptional activation of beta-R1 by IFN-beta required competent TYK2 kinase. These studies indicate that the catalytic function of TYK2 is required for IFN-beta-mediated induction of beta-R1. Catalytic TYK2 is the first identified component in an accessory signaling pathway that supplements ISGF3/interferon-stimulated response element signaling for gene induction by type I IFNs.

Catalysis↗