Handbook of Cell Signaling
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Handbook of Cell Signaling, Three-Volume Set
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Handbook of Cell Signaling
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No missing pages. See all condition definitions - opens in a new window or tab. Steroid receptors, on the other hand, may be repressive on gene expression when their transactivation domain is hidden. Receptor activity can be enhanced by phosphorylation of serine residues at their N-terminal as a result of another signal transduction pathway, a process called crosstalk. Retinoic acid receptors are another subset of nuclear receptors. They can be activated by an endocrine-synthesized ligand that entered the cell by diffusion, a ligand synthesised from a precursor like retinol brought to the cell through the bloodstream or a completely intracellularly synthesised ligand like prostaglandin.
These receptors are located in the nucleus and are not accompanied by HSPs. They repress their gene by binding to their specific DNA sequence when no ligand binds to them, and vice versa. Certain intracellular receptors of the immune system are cytoplasmic receptors; recently identified NOD-like receptors NLRs reside in the cytoplasm of some eukaryotic cells and interact with ligands using a leucine-rich repeat LRR motif similar to TLRs. Second messengers are the substances that enter the cytoplasm and act within the cell to trigger a response.
In essence, second messengers serve as chemical relays from the plasma membrane to the cytoplasm, thus carrying out intracellular signal transduction. The release of calcium ions from the endoplasmic reticulum into the cytosol results in its binding to signaling proteins that are then activated; it is then sequestered in the smooth endoplasmic reticulum  and the mitochondria. The nature of calcium in the cytosol means that it is active for only a very short time, meaning its free state concentration is very low and is mostly bound to organelle molecules like calreticulin when inactive.
Calcium is used in many processes including muscle contraction, neurotransmitter release from nerve endings, and cell migration. The three main pathways that lead to its activation are GPCR pathways, RTK pathways, and gated ion channels; it regulates proteins either directly or by binding to an enzyme. Lipophilic second messenger molecules are derived from lipids residing in cellular membranes; enzymes stimulated by activated receptors activate the lipids by modifying them. Examples include diacylglycerol and ceramide , the former required for the activation of protein kinase C.
Nitric oxide NO acts as a second messenger because it is a free radical that can diffuse through the plasma membrane and affect nearby cells. It is synthesised from arginine and oxygen by the NO synthase and works through activation of soluble guanylyl cyclase , which when activated produces another second messenger, cGMP. NO can also act through covalent modification of proteins or their metal co-factors; some have a redox mechanism and are reversible.
It is toxic in high concentrations and causes damage during stroke , but is the cause of many other functions like relaxation of blood vessels, apoptosis , and penile erections. In addition to nitric oxide, other electronically activated species are also signal-transducing agents in a process called redox signaling. Examples include superoxide , hydrogen peroxide , carbon monoxide , and hydrogen sulfide.
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Redox signaling also includes active modulation of electronic flows in semiconductive biological macromolecules. Gene activations  and metabolism alterations  are examples of cellular responses to extracellular stimulation that require signal transduction. Gene activation leads to further cellular effects, since the products of responding genes include instigators of activation; transcription factors produced as a result of a signal transduction cascade can activate even more genes.
Hence, an initial stimulus can trigger the expression of a large number of genes, leading to physiological events like the increased uptake of glucose from the blood stream  and the migration of neutrophils to sites of infection. The set of genes and their activation order to certain stimuli is referred to as a genetic program. Mammalian cells require stimulation for cell division and survival; in the absence of growth factor , apoptosis ensues. Such requirements for extracellular stimulation are necessary for controlling cell behavior in unicellular and multicellular organisms; signal transduction pathways are perceived to be so central to biological processes that a large number of diseases are attributed to their disregulation.
Three basic signals determine cellular growth:. The combination of these signals are integrated in an altered cytoplasmic machinery which leads to altered cell behaviour. Following are some major signaling pathways, demonstrating how ligands binding to their receptors can affect second messengers and eventually result in altered cellular responses.
The earliest notion of signal transduction can be traced back to , when Claude Bernard proposed that ductless glands such as the spleen , the thyroid and adrenal glands , were responsible for the release of "internal secretions" with physiological effects. The discovery of nerve growth factor by Rita Levi-Montalcini in , and epidermal growth factor by Stanley Cohen in , led to more detailed insights into the molecular basis of cell signaling, in particular growth factors.
In , Martin Rodbell examined the effects of glucagon on a rat's liver cell membrane receptor. He noted that guanosine triphosphate disassociated glucagon from this receptor and stimulated the G-protein , which strongly influenced the cell's metabolism. Thus, he deduced that the G-protein is a transducer that accepts glucagon molecules and affects the cell. Thus, the characterization of RTKs and GPCRs led to the formulation of the concept of "signal transduction", a word first used in The term first appeared in a paper's title in From Wikipedia, the free encyclopedia.
This article is about signaling at the cellular level. For systemic signal transduction, see Transduction physiology. Main article: Stimulus physiology. Main article: Ligand biochemistry. Main article: Mechanotransduction.
14 editions of this work
Main article: Osmoreceptor. Main article: Thermoception. Main article: Visual phototransduction. Main article: G protein—coupled receptor. Main article: Integrin. Main article: Toll-like receptor. Main article: Ligand-gated ion channel. Main article: Intracellular receptor. Main article: Second messenger system.
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New York: Garland Science. June EMBO Reports. Maxwell March Annual Review of Neuroscience. International Journal of Biometeorology. Signal transmission in the cochlear hair cell-nerve junction". Archives of Otolaryngology. Biophysics of Structure and Mechanism. Signal transduction. Academic Press. Intracellular signaling peptides and proteins.