Signal transduction

About: Signal transduction is a research topic. Over the lifetime, 122628 publications have been published within this topic receiving 8209258 citations. The topic is also known as: GO:0007165.

Regulation of Gliogenesis in the Central Nervous System by the JAK-STAT Signaling Pathway

Abstract: A mechanism by which members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor cytokine family regulate gliogenesis in the developing mammalian central nervous system was characterized. Activation of the CNTF receptor promoted differentiation of cerebral cortical precursor cells into astrocytes and inhibited differentiation of cortical precursors along a neuronal lineage. Although CNTF stimulated both the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Ras-mitogen-activated protein kinase signaling pathways in cortical precursor cells, the JAK-STAT signaling pathway selectively enhanced differentiation of these precursors along a glial lineage. These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development.

T Lymphocyte Costimulation Mediated by Reorganization of Membrane Microdomains

Abstract: Although dispensable, costimulation through CD28 facilitates activation of naive T lymphocytes. CD28 engagement led to the redistribution and clustering of membrane and intracellular kinase-rich raft microdomains at the site of T cell receptor (TCR) engagements. Although not affecting TCR down-regulation, this process led to higher and more stable tyrosine phosphorylation of several substrates and higher consumption of Lck. These results may provide a general mechanism for amplifying receptor signaling by reorganization of membrane microdomains.

Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis

Abstract: Binding of Fas ligand or an agonistic anti-Fas antibody induces apoptosis in Fas-bearing cells. The interleukin-1Beta-converting enzyme (ICE) is a cysteine protease that is involved in apoptosis induced by various stimuli, including Fas-mediated apoptosis. Several ICE homologues have been identified, and these are subdivided into three groups (ICE-, CPP32-, and Ich-1-like proteases). We show here that specific inhibitors of ICE- or CPP32-like proteases can inhibit Fas-mediated apoptosis. Transient ICE-like activity was found in the cytosolic fraction of Fas-activated cells, whereas ICE-dependent, CPP32-like activity gradually accumulated in the cytosol. Cell lysates from mouse lymphoma supplemented with either recombinant ICE or CPP32 induced apoptosis of nuclei. The CPP32 inhibitor inhibited ICE- or CPP32-induced apoptosis in the cell-free system, whereas the ICE-inhibitor only inhibited ICE-induced apoptosis. Cell extracts from thymocytes from ICE-null mice induced apoptosis in the cell-free system when it was supplemented with CPP32. These results indicate that Fas sequentially activates ICE- and CPP32-like proteases, and that downstream CPP32, together with a component(s) in the cytoplasm, causes apoptosis of nuclei.

Controlling Natural Killer Cell Responses: Integration of Signals for Activation and Inhibition

Abstract: Understanding how signals are integrated to control natural killer (NK) cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress, and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I-specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibito...

Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun.

Abstract: THE stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-termi-nal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-α and interleukin-β (refs 1, 2). SAPK phosphorylation of c-Jun probably activates the c-Jun transactivation function3. SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway1. We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs)4. SEK1 is a potent activator of the SAPKs in vitro and in vivo. An inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK pathway. Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor.